Impaired Movement Research Articles

Increased beta synchronization underlies perception-action hyperbinding in functional movement disorders.

Functional movement disorders are amongst the most common and disabling neurological conditions, placing a significant burden on the healthcare system. Despite the frequency and importance of functional movement disorders, our understanding of the underlying pathophysiology is limited, hindering the development of causal treatment options. Traditionally, functional movement disorders were considered as a psychiatric condition, associated with involuntary movements triggered by psychological stressors. Recent neurophysiological studies have unveiled cognitive alterations in affected individuals, suggesting that functional movement disorders might be better characterized by overarching neural principles governing cognitive functions. For instance, recent research has shown that the retrieval of stimulus-response bindings is altered in patients with functional movement disorders. Building upon these recent findings, our study delves into whether the initial integration of stimulus and response information is also disrupted in patients with functional movement disorders. To accomplish this, we reanalysed previously collected EEG data using refined analysis methods that provide insights into oscillatory activity and functional neuroanatomy associated with the integration of stimulus-response bindings. Our results demonstrate that post-movement beta synchronization (i) predicts behavioural stimulus-response binding and (ii) is significantly increased in patients with functional movement disorders compared to healthy controls. Utilizing beamformer analysis, we localized the difference effect to a cluster centred around the left supplementary motor area and the correlation effect to the right supplementary motor area. Extending beyond recent research that focused on the retrieval of stimulus-response bindings, our present findings reveal that the integration of stimulus and response information is already impaired in patients with functional movement disorders. These results uncover a phenomenon of hyperbinding between perception and action, which may represent a fundamental mechanism contributing to the movement impairments in patients with functional movement disorders.

Effectiveness of intraoperative nerve monitoring in reducing rates of recurrent laryngeal nerve injury in aerodigestive and cardiovascular pediatric surgery

ObjectiveTo investigate the effectiveness of intraoperative nerve monitoring at decreasing vocal fold movement impairment in children undergoing at-risk procedures. BackgroundChildren undergoing aerodigestive or cardiovascular procedures are at risk for recurrent laryngeal nerve injury, leading to vocal fold movement impairment. Although intraoperative nerve monitoring has been shown to decrease recurrent laryngeal nerve injury in adults, there is paucity of data in children. MethodsThis was a retrospective, single-center cohort study of children who underwent airway, esophageal, or great vessel surgery between 2018 and 2023. Vocal fold movement impairment was evaluated with pre- and postoperative awake flexible fiberoptic laryngoscopy. Vocal fold movement impairment rates and associated characteristics were compared between those with and without intraoperative nerve monitoring. ResultsAmong 387 children undergoing 426 at-risk procedures, intraoperative nerve monitoring was used in 72.1% (n = 307) of procedures. Intraoperative nerve monitoring significantly reduced postoperative vocal fold movement impairment compared with those without (11.4% vs 20.2%, P = .019, 43.6% relative risk reduction, number needed to treat: 12). In children with a pre-existing vocal fold movement impairment (n = 79, 18.5%), intraoperative nerve monitoring provided enhanced protection (vocal fold movement impairment 7.8% with intraoperative nerve monitoring compared with 25% without, P = .046, 68.6% relative risk reduction, number needed to treat: 3). Bilateral vocal fold movement impairment was 14 times more likely without intraoperative nerve monitoring (1.8% overall, 0.3% with intraoperative nerve monitoring, 5.6% without; 95% confidence interval 1.6–123.2; P = .006). Increasing intraoperative nerve monitoring use correlated with decreasing vocal fold movement impairment rates year over year (P = .046). Multivariable logistic regression demonstrated intraoperative nerve monitoring to remain significantly associated with reduced risk of vocal fold movement impairment (odds ratio, 0.48; 95% confidence interval, 0.26–0.85; P = .013). ConclusionIntraoperative nerve monitoring in children seems effective at decreasing recurrent laryngeal nerve injury and consequently vocal fold movement impairment. Intraoperative nerve monitoring should be considered in children undergoing cervicothoracic or cardiothoracic procedures, especially in those with preoperative vocal fold movement impairment.

Esophageal Dysmotility in Multiple System Atrophy: A Retrospective Cross-Sectional Study.

Background/Objective: Multiple system atrophy (MSA) is often associated with dysphagia and esophageal dysmotility (ED). However, ED in patients with MSA is poorly understood. To assess the relationship between ED, dysphagia, and other clinical findings in such patients and investigate the details of ED in MSA using high-resolution manometry (HRM). Methods: Patients from The University of Tokyo Hospital with MSA who underwent swallowing examinations, esophagography, and HRM between 2017 and 2022 were enrolled. A retrospective chart review of patients' backgrounds, swallowing function, and esophageal motility was performed. ED was evaluated using the Chicago Classification version 4.0. Results: Seventy-four patients with MSA were identified. The median age was 64 years, 48 patients (65%) were male, and the cerebellar variant type was predominant (69%). Abnormal upper esophageal sphincter (UES) resting pressure was observed in 34 patients (46%) and intraesophageal stasis in 65 (88%). High-severity MSA was a risk factor for developing dysphagia, vocal fold movement impairment, and abnormal UES function (p < 0.05). However, no overt clinical risk factors for ED were identified. Various types of ED were detected using HRM, and ineffective esophageal motility was the most frequent disorder. Conclusions: ED is a common occurrence in patients with MSA. Although a high-severity MSA may be a risk factor for developing dysphagia and vocal fold motion impairment, ED can occur regardless of clinical severity. Since ED is rarely detected based on subjective symptoms, careful evaluation of esophageal motility by esophagography or HRM is warranted in patients with MSA.

Stage-dependent role of interhemispheric pathway for motor recovery in primates

Whether and how the non-lesional sensorimotor cortex is activated and contributes to post-injury motor recovery is controversial. Here, we investigated the role of interhemispheric pathway from the contralesional to ipsilesional premotor cortex in activating the ipsilesional sensorimotor cortex and promoting recovery after lesioning the lateral corticospinal tract at the cervical cord, by unidirectional chemogenetic blockade in macaques. The blockade impaired dexterous hand movements during the early recovery stage. Electrocorticographical recording showed that the low frequency band activity of the ipsilesional premotor cortex around movement onset was decreased by the blockade during the early recovery stage, while it was increased by blockade during the intact state and late recovery stage. These results demonstrate that action of the interhemispheric pathway changed from inhibition to facilitation, to involve the ipsilesional sensorimotor cortex in hand movements during the early recovery stage. The present study offers insights into the stage-dependent role of the interhemispheric pathway and a therapeutic target in the early recovery stage after lesioning of the corticospinal tract.

CHALLENGE IN TREATING OPTIC NEURITIS IN PATIENT WITH CEREBRAL TOXOPLASMOSIS RELATED TO IMMUNOCOMPROMISED CONDITION

Introduction: This study aimed to discuss the prognosis of optic neuritis in a patient with cerebral toxoplasmosis related to an immunocompromised condition. Case Report: A 28-year-old female complained of blurred vision and double vision 2 weeks before admission, accompanied by headache, low extremities weakness, dysphonia, and dysphagia. Visual acuity of both eyes was 6/30 and worsened to 6/60 in a couple of days. Anterior segment examination revealed anisocoria pupil, and RAPD was positive in the left eye. Funduscopic examination showed a blurry margin and hyperemia of the optic nerve head. There was impaired eye movement, indicating oculomotor and abducens nerve palsies. High titer of IgG Antibody Toxoplasma (264) and very low titer of CD4 (&lt;50) with non-reactive HIV rapid test were found in laboratory findings. Multiple ring enhancement was shown in MRI finding. Unfortunately, patient passed away during hospitalization due to respiratory failure. Discussion: Toxoplasmosis-associated optic neuritis is rare and usually becomes potentially serious. Although parasite detection by microscopy and bioassay is considered the gold standard for the diagnosis of toxoplasmosis, clinical diagnosis relies more on serological examination methods. The high proportion of deaths from this disease is mostly caused by late diagnosis of the infection. Conclusion: Optic neuritis that accompanied by systemic disorders needs special attention and comprehensive treatment among multidisciplinary divisions, especially in the immunocompromised condition. Early detection and primary prevention are important to improve prognosis and survival rate.

Intraspinal microstimulation of the ventral horn has therapeutically relevant cross-modal effects on nociception.

Electrical stimulation of spinal networks below a spinal cord injury is a promising approach to restore functions compromised by inadequate and/or inappropriate neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared descending motor pathways and spinal motoneurons rendered dormant after being severed from their inputs by lesion. Less well understood is whether spinal stimulation is also capable of reducing neural transmission in pathways made pathologically overactive by spinal cord injury. Debilitating spasms, spasticity and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. Whereas spasms and spasticity can often be managed pharmacologically, spinal cord injury-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from aetiologies other than spinal cord injury, and the limited evidence available to date suggests that it holds considerable promise for reducing spinal cord injury-related neuropathic pain, as well. Spinal stimulation for pain amelioration has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for rehabilitation of movement impairments. Thus, we hypothesize that spinal stimulation intended to increase the ability to move voluntarily may simultaneously reduce transmission in spinal pain pathways. To test this hypothesis, we coupled a rat model of incomplete thoracic spinal cord injury, which results in moderate to severe bilateral movement impairments and spinal cord injury-related neuropathic pain, with in vivo electrophysiological measures of neural transmission in networks of spinal neurons integral to the development and persistence of the neuropathic pain state. We find that when intraspinal microstimulation is delivered to the ventral horn with the intent of enhancing voluntary movement, transmission through nociceptive specific and wide dynamic range neurons is significantly depressed in response to pain-related sensory feedback. By comparison, spinal responsiveness to non-pain-related sensory feedback is largely preserved. These results suggest that spinal stimulation paradigms could be intentionally designed to afford multi-modal therapeutic benefits, directly addressing the diverse, intersectional rehabilitation goals of people living with spinal cord injury.

SLC30A9: an evolutionarily conserved mitochondrial zinc transporter essential for mammalian early embryonic development

SLC30A9 (ZnT9) is a mitochondria-resident zinc transporter. Mutations in SLC30A9 have been reported in human patients with a novel cerebro-renal syndrome. Here, we show that ZnT9 is an evolutionarily highly conserved protein, with many regions extremely preserved among evolutionarily distant organisms. In Drosophila melanogaster (the fly), ZnT9 (ZnT49B) knockdown results in acutely impaired movement and drastic mitochondrial deformation. Severe Drosophila ZnT9 (dZnT9) reduction and ZnT9-null mutant flies are pupal lethal. The phenotype of dZnT9 knockdown can be partially rescued by mouse ZnT9 expression or zinc chelator TPEN, indicating the defect of dZnT9 loss is indeed a result of zinc dyshomeostasis. Interestingly, in the mouse, germline loss of Znt9 produces even more extreme phenotypes: the mutant embryos exhibit midgestational lethality with severe development abnormalities. Targeted mutagenesis of Znt9 in the mouse brain leads to serious dwarfism and physical incapacitation, followed by death shortly. Strikingly, the GH/IGF-1 signals are almost non-existent in these tissue-specific knockout mice, consistent with the medical finding in some human patients with severe mitochondrial deficiecny. ZnT9 mutations cause mitochondrial zinc dyshomeostasis, and we demonstrate mechanistically that mitochondrial zinc elevation quickly and potently inhibits the activities of respiration complexes. These results reveal the critical role of ZnT9 and mitochondrial zinc homeostasis in mammalian development. Based on our functional analyses, we finally discussed the possible nature of the so far identified human SLC30A9 mutations.

Swallowing Safety after Remote sub-total Esophagectomy: How Important is Tongue Pressure?

The factors related to oropharyngeal dysphagia after remote esophagectomy (greater than five months) remain unclear. This study aimed to assess patient perception of dysphagia, maximum anterior isometric pressure (MAIP), maximum posterior isometric pressure (MPIP), lingual swallowing pressure (LSP) and radiographic physiological components of the oral and pharyngeal phases of swallowing in patients who are post remote sub-total esophagectomy (SE). Patient perception of dysphagia was assessed using the Eating Assessment Tool (EAT-10). MAIP, MPIP, and LSP were measured using the Iowa Oral Performance Instrument. Videofluoroscopy was used to assess the physiologic components of swallowing with the Modified Barium Swallow Impairment Profile (MBSImP) and the Penetration-Aspiration Scale (PAS). Ten patients were included in the study (53.2% male; mean age 54.5 ± 18.0). The mean postoperative time was 30 months (range, 5.0-72 months). Seven patients had elevated EAT-10 scores (> 3). All patients demonstrated impaired oropharyngeal swallowing on at least three MBSImP components (range 3-12) and two patients aspirated (PAS 8). There was a significant difference in MAIP values when comparing patients with normal versus impaired laryngeal elevation and epiglottic movement (p < 0.001). MPIP values were significantly different in patients with normal versus impaired epiglottic movement as well as normal versus elevated PAS scores (p < 0.001). Decreased lingual pressure and physiological changes in swallowing coexist after SE. Our results indicate that the decrease in tongue strength may be one of the factors related to unsafe swallow. The assessment of lingual pressure provides diagnostic value and should be incorporated as part of a comprehensive assessment in this population.

Stimulated Vocal Fold Immobility After Vagal Nerve Stimulator Placement: A Case Series.

Vagal nerve stimulator (VNS) implantation is a vital therapy for epilepsy refractory to other treatments; however, it is associated with a very high rate of voice changes. Relatively few of these patients are evaluated for vocal fold motion impairments. In this series, we evaluate 5 such patients with a novel phenotype of forced abduction with VNS stimulation. Retrospective case series. Five patients with a VNS implant who underwent operative direct or in-office rigid laryngoscopy and had vocal fold motion impairment associated with VNS activation are included. All 5 patients had vocal fold mobility with VNS off and a fixed with activation. All patients exhibited vocal fold abduction with VNS activation. Patient 2 has since undergone laryngeal reinnervation, which helped her intermittent dysphonia but left a small glottic gap. A type 1 thyroplasty corrected this gap and improved her voice further. Patient 3 has undergone laryngeal reinnervation for which early results show improvement in perceptual and patient reported outcomes. Patients 4 and 5 have both undergone laryngeal reinnervation with improvement in voice. Previous reported cases of stimulated immobility associated with VNS use describe only adduction of the vocal fold. This series expands the previous work showing the VNS activation can also cause stimulated immobility in an abducted position, for which reinnervation and other medialization procedures offer promising treatment.

Association of medullary reticular formation ventral part with spasticity in mice suffering from photothrombotic stroke

Strokes cause spasticity via stretch reflex hyperexcitability in the spinal cord, and spastic paralysis due to involuntary muscle contraction in the hands and fingers can severely restrict skilled hand movements. However, the underlying neurological mechanisms remain unknown. Using a mouse model of spasticity after stroke, we demonstrate changes in neuronal activity with and without electrostimulation of the afferent nerve to induce the stretch reflex, measured using quantitative activation-induced manganese-enhanced magnetic resonance imaging. Neuronal activity increased within the ventral medullary reticular formation (MdV) in the contralesional brainstem during the acute post-stroke phase, and this increase was characterised by activation of circuits involved in spasticity. Interestingly, ascending electrostimulation inhibited the MdV activity on the stimulation side in normal conditions.Moreover, immunohistochemical staining showed that, in the acute phase, the density of GluA1, one of the α-amino-3 hydroxy‑5 methyl -4 isoxazolepropionic acid receptor (AMPAR) subunits, at the synapses of MdV neurons was significantly increased. In addition, the GluA1/GluA2 ratio in these receptors was altered at 2 weeks post-stroke, confirming homeostatic plasticity as the underlying mechanisms of spasticity. These results provide new insights into the relationship between impaired skilled movements and spasticity at the acute post-stroke phase.

New Perspectives for Spinal Cord Stimulation in Parkinson's Disease-Associated Gait Impairment: A Systematic Review.

Parkinson's Disease is a neurodegenerative disorder manifesting itself as a hypokinetic movement impairment with postural instability and gait disturbance. In case of failure and/or limited response, deep brain stimulation has been established as an alternative and effective treatment modality. However, a subset of PD patients with gait impairment represents a therapeutic challenge. A systematic review (2000-2023) was performed using PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases to determine the efficacy, stimulation waveform/parameters, spine level, and outcome measures of spinal cord stimulation using different waveforms in PD patients with and without chronic pain. Spinal cord stimulation responsiveness was assessed within the pre-defined follow-up period in three groups (short-term follow-up = 0-3 months; intermediate follow-up = 3-12 months; and long-term follow-up = more than 12 months). In addition, we briefly outline alternative neurostimulation therapies and the most recent developments in closed-loop spinal cord stimulation relevant to PD. In summary, 18 publications and 70 patients from uncontrolled observational trials were included, with low-quality evidence and conflicting findings. First and foremost, the currently available data do not support the use of spinal cord stimulation to treat PD-related gait disorders but have confirmed its usefulness for PD-associated chronic pain.

Reliability and concurrent validity of the Active Movement Scale (AMS) in adults with musculoskeletal disorders.

The Active Movement Scale (AMS) is a brief screen for identifying movement impairments affecting functional task performance. To assess inter-rater reliability, test-retest reliability, floor and ceiling effects, and concurrent validity of the AMS in adults with musculoskeletal disorders. Fifty-five subjects (mean age: 61.3±15.3 years) transitioning from physical therapy attended two sessions. The 14-item AMS was assessed by two therapists, resulting in a total score (AMST) and two sub-scores: upper body (AMSU) and lower body (AMSL). Moreover, subjects completed PROMIS Physical Function-10a (PPF), Lifestyle Physical Function (LPF), Cardio Activity Level (CAL) surveys, Two Square Agility Test (TSAT), WorkAbility Rate of Manipulation Turning (WRMT) and Placing (WRMP), Grip Strength (GS), 10-Meter Walk Usual (GSU) and Fast (GSF) pace, and Grooved Pegboard Placing (GPP) and Remove (GPR) tests. Inter-rater reliability coefficients for AMST, AMSU, and AMSL were 0.96, 0.92, and 0.96, respectively, with individual item reliability ranging from 0.58 to 1.0. Test-retest reliability for these assessments yielded coefficients of 0.93, 0.84, and 0.94, with individual item reliability ranging from 0.47 to 0.88. No floor effects were observed, but mild ceiling effects were noted. AMST showed a high correlation with LPF (r = 0.72) and moderate correlation with PPF (r = 0.64) surveys. AMSU had moderate correlations with GPP (r = 0.61) and WRMP (r = 0.57) tests, while AMSL correlated moderately with GSF (r = 0.55) and TSAT (r = 0.50) tests. This study provides evidence of the reliability and validity of AMS in adults with musculoskeletal disorders to support transitions between rehabilitation and fitness programs.

Exploring the Feasibility of Bidirectional Control of Beta Oscillatory Power in Healthy Controls as a Potential Intervention for Parkinson's Disease Movement Impairment.

Neurofeedback (NF) is a promising intervention for improvements in motor performance in Parkinson's disease. This NF pilot study in healthy participants aimed to achieve the following: (1) determine participants' ability to bi-directionally modulate sensorimotor beta power and (2) determine the effect of NF on movement performance. A real-time EEG-NF protocol was used to train participants to increase and decrease their individual motor cortex beta power amplitude, using a within-subject double-blind sham-controlled approach. Movement was assessed using a Go/No-go task. Participants completed the NASA Task Load Index and provided verbal feedback of the NF task difficulty. All 17 participants (median age = 38 (19-65); 10 females) reliably reduced sensorimotor beta power. No participant could reliably increase their beta activity. Participants reported that the NF task was challenging, particularly increasing beta. A modest but significant increase in reaction time correlated with a reduction in beta power only in the real condition. Findings suggest that beta power control difficulty varies by modulation direction, affecting participant perceptions. A correlation between beta power reduction and reaction times only in the real condition suggests that intentional beta power reduction may shorten reaction times. Future research should examine the minimum beta threshold for meaningful motor improvements, and the relationship between EEG mechanisms and NF learning to optimise NF outcomes.

Delphi study for developing a checklist of adverse events associated with acupotomy

BackgroundAcupotomy, a more invasive procedure than acupuncture, involves the use of a thicker needle with an integrated knife at the tip, necessitating safety research. We aimed to define relevant adverse events (AEs) and create a standardized form of the ACUPOtomy-related AEs CHECKlist (ACUPOCHECK). MethodsBefore conducting the Delphi process, a systematic review and pilot prospective study were conducted to gather information on previously reported AEs. Using these data, pilot versions of the ACUPOCHECK and Delphi questionnaires were developed. The Delphi questionnaire involved selecting types of AE for inclusion, establishing separate criteria for acupotomy-related AEs, and achieving a consensus on AE assessment. Thirteen Korean doctors with experience in acupotomy or AE research were recruited to participate in each Delphi round. Consensus was considered to have been reached if the critical value for the content validity ratio met or exceeded 0.538. ResultsThe final ACUPOCHECK was developed using four rounds of the Delphi method and one face-to-face consensus meeting. It included 12 local AEs (pain, hemorrhage, bruise, hematoma, edema, pruritus, rash, infection, nerve damage, dysesthesia, movement impairment, and pneumothorax) and 14 systemic AEs (disease aggravation, needle fatigue, sleepiness, procedural nausea, procedural vomiting, procedural headache, procedural dizziness, sweating, procedural shock, syncope, dyspnea, procedural pain, sleep disorder, and postprocedural infection). Separate criteria were established for pain, hemorrhage and bruising: pain was defined as pain that occurrs during daily activities and persists for longer than 72 h, hemorrhage as bleeding that continues for ≥ 3 min despite pressure application, and bruising as having a bruise with a diameter of ≥ 3 cm. Open-ended descriptions were allowed for AEs not covered by the checklist, and severity and causality were assessed using the Common Terminology Criteria for Adverse Events and modified World Health Organization-Uppsala Monitoring Center criteria. ConclusionACUPOCHECK provides a standardization framework that can help research on traditional practices as well as new tools and techniques that are more invasive and may cause more severe AEs. Subsequent studies will use ACUPOCHECK to develop rational safety guidelines for acupotomy techniques.Please cite this article as: Jun H, Lee H, Yoon SH, Kwon CY, Jeon D, Lee JH, Leem J. Delphi study for developing a checklist of adverse events associated with acupotomy. J Integr Med. 2024; 22(5): 579–587.

Potential Therapeutic Approach using Aromatic l-amino Acid Decarboxylase and Glial-derived Neurotrophic Factor Therapy Targeting Putamen in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative illness characterized by specific loss of dopaminergic neurons, resulting in impaired motor movement. Its prevalence is twice as compared to the previous 25 years and affects more than 10 million individuals. Lack of treatment still uses levodopa and other options as disease management measures. Treatment shifts to gene therapy (GT), which utilizes direct delivery of specific genes at the targeted area. Therefore, the use of aromatic L-amino acid decarboxylase (AADC) and glial-derived neurotrophic factor (GDNF) therapy achieves an effective control to treat PD. Patients diagnosed with PD may experience improved therapeutic outcomes by reducing the frequency of drug administration while utilizing provasin and AADC as dopaminergic protective therapy. Enhancing the enzymatic activity of tyrosine hydroxylase (TH), glucocorticoid hormone (GCH), and AADC in the striatum would be useful for external L-DOPA to restore the dopamine (DA) level. Increased expression of glutamic acid decarboxylase (GAD) in the subthalamic nucleus (STN) may also be beneficial in PD. Targeting GDNF therapy specifically to the putaminal region is clinically sound and beneficial in protecting the dopaminergic neurons. Furthermore, preclinical and clinical studies supported the role of GDNF in exhibiting its neuroprotective effect in neurological disorders. Another Ret receptor, which belongs to the tyrosine kinase family, is expressed in dopaminergic neurons and sounds to play a vital role in inhibiting the advancement of PD. GDNF binding on those receptors results in the formation of a receptor-ligand complex. On the other hand, venous delivery of recombinant GDNF by liposome-based and encapsulated cellular approaches enables the secure and effective distribution of neurotrophic factors into the putamen and parenchyma. The current review emphasized the rate of GT target GDNF and AADC therapy, along with the corresponding empirical evidence.

Analysis of 1782 Pediatric Hoarseness Cases: A Clinical Retrospect Study

ObjectiveThis study aims to clarify the clinical characteristics of pediatric voice disorders. MethodsThe clinical data of 1,782 pediatric patients presenting with voice disorders were retrospectively analyzed. These cases were categorized into four age-based cohorts: 0–3 years, 4–7 years, 8–11 years, and 12–15 years. Variables such as gender disparities, laryngoscopic manifestation, disease types, and acoustic parameters were thoroughly examined. ResultsA total of 1,782 children with acoustic hoarseness were included in this study, comprising 1,325 males and 457 females. When the sex ratio among the children in each group was compared, males were found to outnumber females. A notable male predominance was observed across all age groups.Laryngoscopic results revealed that the most prevalent condition was vocal cord nodules (1,363 cases, 76.48%), followed by vocal cord polyps (271 cases, 15.20%). Other diseases included laryngeal papillomas, vocal fold movement impairment, vocal cord cysts, functional dysphonia, leukoplakia of the vocal cords, and benign laryngeal tumors such as laryngeal amyloidosis and subglottic granular cell tumors. Among these, adenoid hypertrophy was presented in 382 children (21.44%). Additionally, the Reflux Finding Score (RFS) was conducted, and 799 cases (44.83%) were found to have a score above 7.The distribution of various diseases across different age groups indicated that children with vocal cord nodules (637 cases, 46.74%), vocal cord polyps (109 cases, 40.22%), and laryngeal papillomas (35, 36.84%) were predominantly found in the 4–7 years age group. Pediatric acute laryngitis (3 cases, 75%) and vocal fold movement impairment (8 cases, 36.36%) were more common in the 0–3 years age group. Functional dysphonia (4 cases, 66.67%) and vocal cord leukoplakia (4 cases, 80%) were mainly observed in the 12–15 years age group, while vocal cord cysts were predominantly seen in the 8–11 years age group (4 cases, 57.14%).A comparative analysis of acoustic parameters among 153 children showed statistically significant differences in jitter, fundamental frequency (F0), voice handicap index (VHI), reflux symptom index (RSI), and reflux finding score (RFS) across different pathologies. ConclusionThis study highlighted that vocal cord nodules, vocal cord polyps, and laryngeal papillomas were the primary causes of pediatric hoarseness, although the possibility of tumors and rare diseases cannot be disregarded. There was a noticeable gender bias towards males, and functional dysphonia was significantly more prevalent in older children.

Absence of motor impairments or pathological changes in TMEM230 knockout rats

Parkinson’s disease (PD), which is the second most common neurodegenerative disorder, is characterized by progressive movement impairment and loss of midbrain dopaminergic neurons in the substantia nigra. Although mutations in TMEM230 are linked to familial PD, the pathogenic mechanism underlying TMEM230-associated PD remains to be elucidated. To explore the effect of TMEM230 depletion in vivo, we created TMEM230 knockout rats using CRISPR-Cas9 technology. TMEM230 knockout rats did not exhibit any core features of PD, including impaired motor function, loss of dopaminergic neurons in the substantia nigra, or altered expression of proteins related to autophagy, the Rab family, or vesicular trafficking. In addition, no glial reactions were observed in TMEM230 knockout rats. These results indicate that depletion of TMEM230 may not lead to dopaminergic neuron degeneration in rats, further supporting that PD-associated TMEM230 mutations lead to dopaminergic neuron death by gain-of-toxic function.

Brain Activity in Visual-Motor Illusions With Enhanced Joint Motion Intensity.

Background Visual-motor illusion (VMI) is a cognitive approach used to evoke kinesthetic sensations. Research suggests that VMI can modulate brain activity depending on the specific joint movement observed. This study aimed to identify differences in brain activity when observing video images of joint movements at different intensities of movement in VMI. Methodology The study included 14 healthy adult participants. Two types of video images were used: pure ankle dorsiflexion movements (Standard-VMI) and ankle dorsiflexion movements with added resistance (Power-VMI). The brain activity measurement protocol employed a block design with one set of 15 seconds rest, 30 seconds VMI task, and 30 seconds follow-up. Each participant performed the VMI task twice, alternating between Standard-VMI and Power-VMI. Brain activity was measured using functional near-infrared spectroscopy, focusing on motor-related regions. Subjective impressions were assessed using visual analog scales (VAS) for kinesthetic illusions. Results The results revealed that Power-VMI stimulated significantly greater brain activity in the premotor and supplementary motor cortex, supramarginal gyrus, and superior parietal lobule compared with Standard-VMI. Power-VMI resulted in higher VAS values for kinesthetic illusion than Standard-VMI. Additionally, a positive correlation was observed between brain activity in the superior parietal lobule and the degree of kinesthetic illusion. Conclusions These findings indicate that Power-VMI enhances both motor-related brain areas and motor-sensory illusions, potentially having a greater impact on improving motor function. This study provides valuable insights for developing VMI interventions for rehabilitation, particularly for individuals with paralysis or movement impairments.

Cerebellar nuclei cells produce distinct pathogenic spike signatures in mouse models of ataxia, dystonia, and tremor.

The cerebellum contributes to a diverse array of motor conditions, including ataxia, dystonia, and tremor. The neural substrates that encode this diversity are unclear. Here, we tested whether the neural spike activity of cerebellar output neurons is distinct between movement disorders with different impairments, generalizable across movement disorders with similar impairments, and capable of causing distinct movement impairments. Using in vivo awake recordings as input data, we trained a supervised classifier model to differentiate the spike parameters between mouse models for ataxia, dystonia, and tremor. The classifier model correctly assigned mouse phenotypes based on single-neuron signatures. Spike signatures were shared across etiologically distinct but phenotypically similar disease models. Mimicking these pathophysiological spike signatures with optogenetics induced the predicted motor impairments in otherwise healthy mice. These data show that distinct spike signatures promote the behavioral presentation of cerebellar diseases.

Alpha Synuclein Toxicity and Non-Motor Parkinson's.

Parkinson's disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population over the age of 60 years. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of alpha synuclein (αSyn)-rich Lewy bodies both manifesting with classical motor signs. αSyn has emerged as a key protein in PD pathology as it can spread through synaptic networks to reach several anatomical regions of the body contributing to the appearance of non-motor symptoms (NMS) considered prevalent among individuals prior to PD diagnosis and persisting throughout the patient's life. NMS mainly includes loss of taste and smell, constipation, psychiatric disorders, dementia, impaired rapid eye movement (REM) sleep, urogenital dysfunction, and cardiovascular impairment. This review summarizes the more recent findings on the impact of αSyn deposits on several prodromal NMS and emphasizes the importance of early detection of αSyn toxic species in biofluids and peripheral biopsies as prospective biomarkers in PD.