Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds

Peripheral administration (oral, intranasal, intraperitoneal, intravenous) of assembled A53T α-synuclein induced synucleinopathy in heterozygous mice transgenic for human mutant A53T α-synuclein (line M83). The same was the case when cerebellar extracts from a case of multiple system atrophy with type II α-synuclein filaments were administered intraperitoneally, intravenously or intramuscularly. We observed abundant immunoreactivity for pS129 α-synuclein in nerve cells and severe motor impairment, resulting in hindlimb paralysis and shortened lifespan. Filaments immunoreactive for pS129 α-synuclein were in evidence. A 70% loss of motor neurons was present five months after an intraperitoneal injection of assembled A53T α-synuclein or cerebellar extract with type II α-synuclein filaments from an individual with a neuropathologically confirmed diagnosis of multiple system atrophy. Microglial cells changed from a predominantly ramified to a dystrophic appearance. Taken together, these findings establish a close relationship between the formation of α-synuclein inclusions in nerve cells and neurodegeneration, accompanied by a shift in microglial cell morphology. Propagation of α-synuclein inclusions depended on the characteristics of both seeds and transgenically expressed protein.

Gross motor function in children with Congenital Zika Syndrome from Rio de Janeiro, Brazil

Congenital Zika Syndrome (CZS) is characterized by many impairments especially in the central nervous system, potentially compromising neurodevelopment and causing significant morbidity in affected children. The aim was to assess gross motor function in children with CZS. This was a cross-sectional investigation nested within a prospective cohort study of children with CZS based in a Brazilian referral hospital in Rio de Janeiro. Between March/2017 and February/2018, we performed gross motor function assessments using the Gross Motor Function Classification (GMFCS) and the Gross Motor Function Measure (GMFM), estimating the mean and standard deviation of GMFM scores among GMFCS groups. The study sample included 72 children, with a median age of 13 months (7–25). Of these, 63 (87.5%) had severe motor impairment, 3 (4%) had moderate impairment, and 6 (8%) had mild impairment. The mean GMFM score for each group was respectively 11.6, 26.1, and 81.6, with statistically significant differences (p-value < 0.001). Severely affected children only achieved head control in the sitting posture when supported. Children with milder forms were able to develop walking skills.Conclusion: Most children with CZS have major motor disabilities and a poor prognosis. Better understanding of limitations and functionality in children with CZS can serve as a prognostic guide in their management. What is Known:• Severe motor impairment was present in 63 (87.5%) children with CZS.• The degree of neurological impairment was inversely associated with motor performance. What is New:• Microcephaly was more frequent among children with severe gross motor function impairment.• Children with CZS have major motor disabilities and a poor prognosis.

Children’s Imaginaries of Robots for Playing With

Children with severe motor impairment due to cerebral palsy have difficulties engaging in play, although they want to play games that typically developing children play. The barriers imposed by motor impairments against engaging in play can be addressed through the use of robots. We aim to identify how children, who have extensive experience of play, imagine what a robot is and what features would make a robot good to play with. Using a qualitative description design, 19 children from urban and rural settings participated in focus groups to draw and talk about the robots they would like to exist. The data were coded and analyzed using a summative approach to content analysis. The findings revealed that the children imagined that a good robot to play with is one that has an anthropomorphic appearance, is tough and strong, has controls, and that is able to move, grab, speak, and play popular children’s games. In particular, the girls imagined that robots should be able to express positive emotions towards children. Age, gender, culture, and the physical environment in which the children lived influenced what they expected to find in a robot for playing with and how they imagined child–robot interactions.

Cerebrolysin Combined with Rehabilitation Enhances Motor Recovery and Prevents Neural Network Degeneration in Ischemic Stroke Patients with Severe Motor Deficits

The objective of this study was to evaluate whether Cerebrolysin combined with rehabilitation therapy supports additional motor recovery in stroke patients with severe motor impairment. This study analyzed the combined data from the two phase IV prospective, multicenter, randomized, double-blind, placebo-controlled trials. Stroke patients were included within seven days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo with standardized rehabilitation therapy. Assessments were performed at baseline, immediately after the treatment course, and 90 days after stroke onset. The plasticity of the motor system was assessed by diffusion tensor imaging and resting state fMRI. In total, 110 stroke patients were included for the full analysis set (Cerebrolysin n = 59, placebo n = 51). Both groups showed significant motor recovery over time. Repeated-measures analysis of varianceshowed a significant interaction between time and type of intervention as measured by the Fugl–Meyer Assessment (p < 0.05). The Cerebrolysin group demonstrated less degenerative changes in the major motor-related white matter tracts over time than the placebo group. In conclusion, Cerebrolysin treatment as an add-on to a rehabilitation program is a promising pharmacologic approach that is worth considering in order to enhance motor recovery in ischemic stroke patients with severe motor impairment.

Diethylene glycol poisoning: report of two cases due to brewery contamination

Context: Diethylene glycol (DEG) is an alcohol used as industrial antifreeze. Poisoning is usually accidental and involves contamination of food and beverage. We report two cases of DEG poisoning (DEGP) resulting from ingestion of beer in 2020. Case report: ACMO, male, 57 year-old, admitted with bilateral visual turbidity complaint. Laboratory showed renal dysfunction (Cr 11 mg/dl, Ur 202 mg/dl), increased anion GAP (AG) and metabolic acidosis. He evolved with amaurosis, facial diplegia, tetraparesis and areflexia. He was discharged after prolonged hospitalization with severe motor impairment, bilateral amaurosis and under dialysis therapy. RJB, 75 year-old alcoholic male patient, reported 600 ml/day ingestion of high-risk beer in the month preceding his hospitalization. He was admitted with nausea, abdominal pain, renal failure (Cr 11 mg/dl, Ur 177 mg/dl), metabolic acidosis and AG 21. He developed bilateral papilla edema, flaccid tetraparesis, areflexia, dysautonomy, respiratory failure and death. Conclusions: DEG metabolites primarily target kidneys and nervous system. Patients shortly develop nephroneural syndrome characterized by acute oligoanuric renal injury with metabolic acidosis and increased AG, associated with peripheral polyneuropathy with involvement of cranial nerves, in addition to optic neuropathy. Due to the poorly available serum dosage, rapid recognition of DEGP is essential to institute early treatment and identification of the source of the intoxication in order to prevent mass poisoning.

Implementation of an SSVEP-based intelligent home service robot system

BACKGROUND: People with severe neuromuscular disorders caused by an accident or congenital disease cannot normally interact with the physical environment. The intelligent robot technology offers the possibility to solve this problem. However, the robot can hardly carry out the task without understanding the subject’s intention as it relays on speech or gestures. Brain-computer interface (BCI), a communication system that operates external devices by directly converting brain activity into digital signals, provides a solution for this. OBJECTIVE: In this study, a noninvasive BCI-based humanoid robotic system was designed and implemented for home service. METHODS: A humanoid robot that is equipped with multi-sensors navigates to the object placement area under the guidance of a specific symbol “Naomark”, which has a unique ID, and then sends the information of the scanned object back to the user interface. Based on this information, the subject gives commands to the robot to grab the wanted object and give it to the subject. To identify the subject’s intention, the channel projection-based canonical correlation analysis (CP-CCA) method was utilized for the steady state visual evoked potential-based BCI system. RESULTS: The offline results showed that the average classification accuracy of all subjects reached 90%, and the online task completion rate was over 95%. CONCLUSION: Users can complete the grab task with minimum commands, avoiding the control burden caused by complex commands. This would provide a useful assistance means for people with severe motor impairment in their daily life.

Dorsolateral prefrontal cortex-based control with an implanted brain–computer interface

The objective of this study was to test the feasibility of using the dorsolateral prefrontal cortex as a signal source for brain–computer interface control in people with severe motor impairment. We implanted two individuals with locked-in syndrome with a chronic brain–computer interface designed to restore independent communication. The implanted system (Utrecht NeuroProsthesis) included electrode strips placed subdurally over the dorsolateral prefrontal cortex. In both participants, counting backwards activated the dorsolateral prefrontal cortex consistently over the course of 47 and 22 months, respectively. Moreover, both participants were able to use this signal to control a cursor in one dimension, with average accuracy scores of 78 ± 9% (standard deviation) and 71 ± 11% (chance level: 50%), respectively. Brain–computer interface control based on dorsolateral prefrontal cortex activity is feasible in people with locked-in syndrome and may become of relevance for those unable to use sensorimotor signals for control.

Motoric impairment versus iron deposition gradient in the subthalamic nucleus in Parkinson’s disease

OBJECTIVEThe objective of this study was to investigate the correlation between the quantitative susceptibility mapping (QSM) signal gradient of the subthalamic nucleus (STN) and motor impairment in patients with Parkinson’s disease (PD).METHODSAll PD patients who had undergone QSM MRI for presurgical deep brain stimulation (DBS) planning were eligible for inclusion in this study. The entire STN and its three functional subdivisions, as well as the adjacent white matter (WM), were segmented and measured. The QSM value difference between the entire STN and adjacent WM (STN-WM), between the limbic and associative regions of the STN (L-A), and between the associative and motor regions of the STN (A-M) were obtained as measures of gradient and were input into an unsupervised k-means clustering algorithm to automatically categorize the overall boundary distinctness between the STN and adjacent WM and between STN subdivisions (gradient blur [GB] and gradient sharp [GS] groups). Statistical tests were performed to compare clinical and image measurements for discrimination between GB and GS groups.RESULTSOf the 39 study patients, 19 were categorized into the GB group and 20 into the GS group, based on quantitative cluster analysis. The GB group had a significantly higher presurgical off-medication Unified Parkinson’s Disease Rating Scale Part III score (51.289 ± 20.741) than the GS group (38.5 ± 16.028; p = 0.037). The GB group had significantly higher QSM values for the STN and its three subdivisions and adjacent WM than those for the GS group (p < 0.01). The GB group also demonstrated a significantly higher STN-WM gradient in the right STN (p = 0.01). The GB group demonstrated a significantly lower L-A gradient in both the left and the right STN (p < 0.02).CONCLUSIONSAdvancing PD with more severe motor impairment leads to more iron deposition in the STN and adjacent WM, as shown in the QSM signal. Loss of the STN inner QSM signal gradient should be considered as an image marker for more severe motor impairment in PD patients.

The Probability of Choosing Both Hands Depends on an Interaction Between Motor Capacity and Limb-Specific Control in Chronic Stroke

A goal of rehabilitation after stroke is to promote pre-stroke levels of arm use for everyday, frequently bimanual, functional activities. We reasoned that, after a stroke, the choice to use one or both hands for bimanual tasks might depend not only on residual motor capacity but also the specialized demands imposed by the task on the paretic hand. To capture spontaneous, task-specific choices, we covertly observed 50 pre-stroke right-handed chronic stroke survivors (25 left hemisphere damage, LHD) and recorded their hand use strategies for two pairs of bimanual tasks with distinct demands: one with greater precision requirements (photo-album tasks), and another with greater stabilization requirements (letter-envelope tasks). The primary outcome was the choice to use one or both hands. Logistic regression was used to test the hypothesis that the probability of choosing a bimanual strategy would be greater in those with less severe motor impairment and those with LHD. When collapsed across the four subtasks, we found support for this hypothesis. However, notably, the influence of these factors on bimanual choice varied based on task demands. For the photo-album task, the probability of a bimanual strategy was greater for those with LHD compared to RHD, regardless of the degree of motor impairment. For the letter-envelope task, we found a significant interaction between impairment and side of lesion in determining the likelihood of choosing both hands. Therefore, the manner in which side of lesion moderates the effect of impairment on hand use depends on the task.

Model for prompt and effective classification of motion recovery after stroke considering muscle strength and coordination factors

Background Muscle synergies are now widely discussed as a method for evaluating the existence of redundant neural networks that can be activated to enhance stroke rehabilitation. However, this approach was initially conceived to study muscle coordination during learned motions in healthy individuals. After brain damage, there are several neural adaptations that contribute to the recovery of motor strength, with muscle coordination being one of them. In this study, a model is proposed that assesses motion based on surface electromyography (sEMG) according to two main factors closely related to the neural adaptations underlying motor recovery: (1) the correct coordination of the muscles involved in a particular motion and (2) the ability to tune the effective strength of each muscle through muscle fiber contractions. These two factors are hypothesized to be affected differently by brain damage. Therefore, their independent evaluation will play an important role in understanding the origin of stroke-related motor impairments. Results The model proposed was validated by analyzing sEMG data from 18 stroke patients with different paralysis levels and 30 healthy subjects. While the factors necessary to describe motion were stable across heathy subjects, there was an increasing disassociation for stroke patients with severe motor impairment. Conclusions The clear dissociation between the coordination of muscles and the tuning of their strength demonstrates the importance of evaluating these factors in order to choose appropriate rehabilitation therapies. The model described in this research provides an efficient approach to promptly evaluate these factors through the use of two intuitive indexes.