Impaired Coordination Research Articles

CO49 Clinical Efficacy and Safety of Therapeutic Interventions Used in Friedreich Ataxia: A Systematic Review

Friedreich Ataxia (FA) is a rare inherited autosomal recessive disease that causes progressive neurodegenerative changes and disability due to impaired muscle coordination. A systematic literature review (SLR) was conducted to assess the published efficacy and safety of therapeutic interventions in FA.

Dichoptic and Monocular Visual Acuity in Amblyopia

Standard-of-care assessment for children with amblyopia includes measuring amblyopic eye best-corrected visual acuity (AE BCVA) with the fellow eye occluded. By definition, this abolishes the interocular suppression fundamental to amblyopia. Thus, measured AE BCVA may not accurately represent that eye's contribution to natural binocular viewing. We compared dichoptic and monocular AE BCVA and examined whether any differences were associated with eye-hand coordination or reading speed. Cross-sectional study. Dichoptic and monocular AE BCVA of children aged 6-12 years (42 with amblyopia, 24 with recovered normal AE BCVA, 30 control) were measured. Stereoacuity, suppression, eye-hand coordination, and reading speed were also assessed. Overall, 81% of amblyopic children had worse dichoptic than monocular AE BCVA (mean difference=0.15±0.11 logMAR; P < .0001), and 71% of children with recovered normal AE BCVA had worse dichoptic than monocular AE BCVA (mean difference = 0.20±0.17 logMAR, P < .0001). Controls had no significant difference. The difference between dichoptic and monocular AE BCVA was correlated with performance in standardized aiming/catching (r = -0.48, 95% CI -0.72, -0.14) and manual dexterity tasks (r = -0.37, 95% CI -0.62, -0.06), and with reading speed (r = -0.38, 95% CI -0.65, -0.03). Dichoptic AE BCVA deficits were worse than monocular AE BCVA deficits and were associated with reduced stereoacuity and suppression, consistent with the hypothesis that binocular dysfunction plays a role. Further, impaired eye-hand coordination and slow reading were associated with dichoptic, but not monocular, AE BCVA. Some children with amblyopia may benefit from extra time for school tasks requiring eye-hand coordination or reading.

Behavioral Phenotypes of Foxg1 Heterozygous Mice.

FOXG1 syndrome (FS, aka a congenital variant of Rett syndrome) is a recently defined rare and devastating neurodevelopmental disorder characterized by various symptoms, including severe intellectual disability, autistic features, involuntary, and continuous jerky movements, feeding problems, sleep disturbances, seizures, irritability, and excessive crying. FS results from mutations in a single allele of the FOXG1 gene, leading to impaired FOXG1 function. Therefore, in establishing mouse models for FS, it is important to test if heterozygous (HET) mutation in the Foxg1 gene, mimicking genotypes of the human FS individuals, also manifests phenotypes similar to their symptoms. We analyzed HET mice with a null mutation allele in a single copy of Foxg1, and found that they show various phenotypes resembling the symptoms of the human FS individuals. These include increased anxiety in the open field as well as impairment in object recognition, motor coordination, and fear learning and contextual and cued fear memory. Our results suggest that Foxg1 HET mice recapitulate at least some symptoms of the human FS individuals.

Motor dysfunction in Drosophila melanogaster as a biomarker for developmental neurotoxicity

SummaryAdequate alternatives to conventional animal testing are needed to study developmental neurotoxicity (DNT). Here, we used kinematic analysis to assess DNT of known (toluene (TOL) and chlorpyrifos (CPS)) and putative (β-N-methylamino-L-alanine (BMAA)) neurotoxic compounds. Drosophila melanogaster was exposed to these compounds during development and evaluated for survival and adult kinematic parameters using the FlyWalker system, a kinematics evaluation method. At concentrations that do not induce general toxicity, the solvent DMSO had a significant effect on kinematic parameters. Moreover, while TOL did not significantly induce lethality or kinematic dysfunction, CPS not only induced developmental lethality but also significantly impaired coordination in comparison to DMSO. Interestingly, BMAA, which was not lethal during development, induced motor decay in young adult animals, phenotypically resembling aged flies, an effect later attenuated upon aging. Furthermore, BMAA induced abnormal development of leg motor neuron projections. Our results suggest that our kinematic approach can assess potential DNT of chemical compounds.

Haploinsufficiency of a Circadian Clock Gene Bmal1 (Arntl or Mop3) Causes Brain-Wide mTOR Hyperactivation and Autism-like Behavioral Phenotypes in Mice.

Approximately 50–80% of children with autism spectrum disorders (ASDs) exhibit sleep problems, but the contribution of circadian clock dysfunction to the development of ASDs remains largely unknown. The essential clock gene Bmal1 (Arntl or Mop3) has been associated with human sociability, and its missense mutation is found in ASD. Our recent study found that Bmal1-null mice exhibit a variety of autism-like phenotypes. Here, we further investigated whether an incomplete loss of Bmal1 function could cause significant autism-like behavioral changes in mice. Our results demonstrated that heterozygous Bmal1 deletion (Bmal1+/−) reduced the Bmal1 protein levels by ~50–75%. Reduced Bmal1 expression led to decreased levels of clock proteins, including Per1, Per2, Cry 1, and Clock but increased mTOR activities in the brain. Accordingly, Bmal1+/− mice exhibited aberrant ultrasonic vocalizations during maternal separation, deficits in sociability and social novelty, excessive repetitive behaviors, impairments in motor coordination, as well as increased anxiety-like behavior. The novel object recognition memory remained intact. Together, these results demonstrate that haploinsufficiency of Bmal1 can cause autism-like behavioral changes in mice, akin to those identified in Bmal1-null mice. This study provides further experimental evidence supporting a potential role for disrupted clock gene expression in the development of ASD.

Subacute tremor and ataxia: Diligence in pursuit of a diagnosis

Case Presentation: A 78-year-old woman presented with a one-month history of progressive tremors and gait instability. She was previously independent and in good health. However, she progressively required help with daily activities due to impaired coordination and increasingly severe tremor in her hands and trunk. Neurologic exam was significant for sustained horizontal nystagmus with a mild rotary component in both directions of lateral gaze (L > R) and low-frequency, high-amplitude tremor in both arms (proximal > distal).

225 A rare case of recurrent unsteadiness due to Miller Fisher syndrome

A 71-year-old male presented to the emergency department with unsteadiness, blurred vision, slurred speech and sensory changes. He had progressive loss of reflexes. After initial horizontal nystagmus he developed bilateral ophthalmoplegia with bilateral ptosis and impaired coordination with an ataxic gait. This was preceded by productive cough and loose stools.The patient was diagnosed with Miller Fisher Syndrome (MFS), with a positive anti-GQ1b antibody and CSF albuminocytologic dissociation supporting the diagnosis. This was the patient’s second episode of MFS. The first had occurred twenty-seven years earlier with a similar presentation and examination findings.This poster then reviews the clinical presentation, management and recurrence of Miller Fisher Syndrome. gavriella.levinson@nhs.net

Acute alcohol intoxication: a clinical overview.

Alcohol is a legal and yet detrimental psychoactive substance, capable of establishing addiction and impacting the physical, mental, social, and economic health of people. Alcohol intake causes a large variety of tissue damages severely impacting the nervous system, digestive and cardiovascular systems and causing oral cavity, oropharyngeal, hypopharyngeal, esophageal, colon-rectal, laryngeal, liver and intrahepatic bile duct, and breast cancers. Alcohol can also play a role in the pathogenesis of diabetes mellitus, cardiomyopathy and hemorrhagic strokes. When drunk during pregnancy it is proved to be responsible for serious damage to fetuses causing a wide range of pathological conditions from miscarriage to Fetal Alcoholic Spectrum Disorder (FASD). Acute ethanol intoxication happens when the amount of alcohol consumed is greater than the disposal capacity of the liver, causing an accumulation of its metabolites displayed by initial dysphoria and disinhibition. Nausea, vomiting, memory loss could happen. Although, it can lead to more serious conditions like impaired speaking, impaired coordination, unstable gait, nystagmus, stupor, or coma. Respiratory depression and death could also happen in such cases. Unfortunately, diagnosis of acute alcohol intoxication is difficult because most of the drinkers deny or minimize their assumption. It is dramatically important to assess when the last intake happened to avoid withdrawal syndrome. Alcohol acute intoxication can be considered a serious harm to health and a relevant issue for healthcare provid-ers working in emergency rooms. Differential diagnosis is crucial to avoid serious outcomes. There is no consensus about therapies for acute intoxication, but supportive and symptomatic treatments were proved effective. The repercussions of alcohol misuse over drinkers' social, familiar, economical and working life enhance the importance of a multidisciplinary approach in such cases.

SLC38A10 Knockout Mice Display a Decreased Body Weight and an Increased Risk-Taking Behavior in the Open Field Test.

The solute carrier 38 family (SLC38) is a family of 11 members. The most common substrate among these are alanine and glutamine, and members are present in a wide range of tissues with important functions for several biological processes, such as liver and brain function. Some of these transporters are better characterized than others and, in this paper, a behavioral characterization of SLC38A10−/− mice was carried out. A battery of tests for general activity, emotionality, motor function, and spatial memory was used. Among these tests, the elevated plus maze, Y-maze, marble burying and challenging beam walk have not been tested on the SLC38A10−/− mice previously, while the open field and the rotarod tests have been performed by the International Mouse Phenotyping Consortium (IMPC). Unlike the results from IMPC, the results from this study showed that SLC38A10−/− mice spend less time in the wall zone in the open field test than WT mice, implying that SLC38A10-deficient mice have an increased explorative behavior, which suggests an important function of SLC38A10 in brain. The present study also confirmed IMPC's data regarding rotarod performance and weight, showing that SLC38A10−/− mice do not have an affected motor coordination impairment and have a lower body weight than both SLC38A10+/− and SLC38A10+/+ mice. These results imply that a complete deficiency of the SLC38A10 protein might affect body weight homeostasis, but the underlying mechanisms needs to be studied further.

Spontaneous partial recovery of striatal dopaminergic uptake despite nigral cell loss in asymptomatic MPTP-lesioned female minipigs

The Göttingen minipig is a large animal with a gyrencephalic brain that expresses –complex behavior, making it an attractive model for Parkinson’s disease research. Here, we investigate the temporal evolution of presynaptic dopaminergic function for 14 months after injections of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the minipig using a multi-tracer longitudinal positron emission tomography (PET) design. We injected seven sedated minipigs with 1–2 mg/kg of MPTP, and two with saline, three times a week over four weeks. We monitored behavioral deficits using a validated motor scale and walking mat. Brains were imaged with (+)-⍺-[11C]-dihydrotetrabenazine ([11C]-DTBZ) and [18F]-dihydroxyphenylalanine ([18F]-FDOPA) PET at baseline and 1, 3, 10 and 14 months after MPTP injection, and immunohistochemistry was used to assess nigral cell loss. The minipigs showed mild bradykinesia and impaired coordination at early timepoints after MPTP. PET revealed decreases of striatal [11C]-DTBZ and [18F]-FDOPA uptake post-MPTP with partial spontaneous recovery of [18F]-FDOPA after 10 months. Postmortem analysis estimated an MPTP-induced nigral loss of 57% tyrosine hydroxylase+ and 43% Nissl-stained cells. Normal motor function despite substantial damage to the dopaminergic system is consistent with prodromal Parkinson’s disease, and offers an opportunity for testing disease-modifying therapies. However, partial spontaneous recovery of dopamine terminal function must be taken into account in future studies.

Acute cannabinoids impair association learning via selectively enhancing synaptic transmission in striatonigral neurons

BackgroundCannabinoids and their derivatives attract strong interest due to the tremendous potential of their psychoactive effects for treating psychiatric disorders and symptoms. However, their clinical application is restricted by various side-effects such as impaired coordination, anxiety, and learning and memory disability. Adverse impact on dorsal striatum-dependent learning is an important side-effect of cannabinoids. As one of the most important forms of learning mediated by the dorsal striatum, reinforcement learning is characterized by an initial association learning phase, followed by habit learning. While the effects of cannabinoids on habit learning have been well-studied, little is known about how cannabinoids influence the initial phase of reinforcement learning.ResultsWe found that acute activation of cannabinoid receptor type 1 (CB1R) by the synthetic cannabinoid HU210 induced dose-dependent impairment of association learning, which could be alleviated by intra-dorsomedial striatum (DMS) injection of CB1R antagonist. Moreover, acute exposure to HU210 elicited enhanced synaptic transmission in striatonigral “direct” pathway medium spiny neurons (MSNs) but not indirect pathway neurons in DMS. Intriguingly, enhancement of synaptic transmission that is also observed after learning was abolished by HU210, indicating cannabinoid system might disrupt reinforcement learning by confounding synaptic plasticity normally required for learning. Remarkably, the impaired response-reinforcer learning was also induced by selectively enhancing the D1-MSN (MSN that selectively expresses the dopamine receptor type 1) activity by virally expressing excitatory hM3Dq DREADD (designer receptor exclusively activated by a designer drug), which could be rescued by specifically silencing the D1-MSN activity via hM4Di DREADD.ConclusionOur findings demonstrate dose-dependent deleterious effects of cannabinoids on association learning by disrupting plasticity change required for learning associated with the striatal direct pathway, which furthers our understanding of the side-effects of cannabinoids and the underlying mechanisms.

Motor Impairments and Dopaminergic Defects Caused by Loss of Leucine-Rich Repeat Kinase Function in Mice.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD), but the pathogenic mechanism underlying LRRK2 mutations remains unresolved. In this study, we investigate the consequence of inactivation of LRRK2 and its functional homolog LRRK1 in male and female mice up to 25 months of age using behavioral, neurochemical, neuropathological, and ultrastructural analyses. We report that LRRK1 and LRRK2 double knock-out (LRRK DKO) mice exhibit impaired motor coordination at 12 months of age before the onset of dopaminergic neuron loss in the substantia nigra (SNpc). Moreover, LRRK DKO mice develop age-dependent, progressive loss of dopaminergic terminals in the striatum. Evoked dopamine (DA) release measured by fast-scan cyclic voltammetry in the dorsal striatum is also reduced in the absence of LRRK. Furthermore, LRRK DKO mice at 20-25 months of age show substantial loss of dopaminergic neurons in the SNpc. The surviving SNpc neurons in LRRK DKO mice at 25 months of age accumulate large numbers of autophagic and autolysosomal vacuoles and are accompanied with microgliosis. Surprisingly, the cerebral cortex is unaffected, as shown by normal cortical volume and neuron number as well as unchanged number of apoptotic cells and microglia in LRRK DKO mice at 25 months. These findings show that loss of LRRK function causes impairments in motor coordination, degeneration of dopaminergic terminals, reduction of evoked DA release, and selective loss of dopaminergic neurons in the SNpc, indicating that LRRK DKO mice are unique models for better understanding dopaminergic neurodegeneration in PD.SIGNIFICANCE STATEMENT Our current study employs a genetic approach to uncover the normal function of the LRRK family in the brain during mouse life span. Our multidisciplinary analysis demonstrates a critical normal physiological role of LRRK in maintaining the integrity and function of dopaminergic terminals and neurons in the aging brain, and show that LRRK DKO mice recapitulate several key features of PD and provide unique mouse models for elucidating molecular mechanisms underlying dopaminergic neurodegeneration in PD.

MO1051: Standardized Simulation Education Program with Summative Assessment on Exchange Procedure of Ultrabag System for Peritoneal Dialysis: Innovations in Practical Recommendations

Abstract BACKGROUND AND AIMS Inexperience in practicing peritoneal dialysis (PD) and lack of standard education program under the instruction of qualified renal nurses are known causes of peritonitis in patients with chronic renal failure [1]. Thus far, the standardized and validated curriculum for Continuous Ambulatory Peritoneal Dialysis (CAPD) training has not been well-established under simulation-based education model [2]. We aimed i) to develop a well-structured and standardized educational training program on exchange procedure of Ultrabag system and ii) to evaluate the degree of acquisition in domains of cognitive (knowledge) and psychomotor (skills) by summative assessment using valid and reliable knowledge evaluation index and performance checklist. METHOD Following an invention of 3D-printed CAPD device, ‘Helping Hands’ in closed system operation, the Renal Unit in the Department of Medicine and Multi-Disciplinary Simulation and Skills Centre (MDSSC) in Queen Elizabeth Hospital (QEH) formulated a standard 5-day CAPD training to equip PD patients with knowledge and skills for safe Ultrabag exchange. In order to optimize training effectiveness and assessment standards, the program was designed with ‘6 (+2 additional) guiding questions’ from the International Society for Peritoneal Dialysis (ISPD) document [3]. Scoring Checklist with specific and relevant items, such as fixation of the connecting catheter, parallel point-to-point connection and procedures in placing disinfection cap, could strengthen internal validity. RESULTS In 2021, 17 CAPD patients with partial impairment in vision (12, 71%) or eye-hand coordination (13, 77%) attended this education program. Post-training assessment showed that participants had improved cognitive knowledge (M = 71%; A Grade (&amp;gt;80 marks) = 5, 29% B Grade (60–80 marks) = 9, 53%; C Grade (&amp;lt;60 marks) = 3, 18%) and psychomotor skills (100% achievement in simulation task). Except for 1 participant who required additional training session and re-assessment, 94% of them passed the simulation examination by completing all procedures without any assistance in one-take. A validated educator-guided scheme of psychomotor skills in proper use of CAPD is recommended with six operational phases: CONCLUSION Repetitive performance in task-specific procedure of bag exchange, coupled with constructive feedback from experienced renal nurse educators and well-validated assessment (with a standardized scoring sheet and checklist), resulted in improved skill performance. The training program, correspondent with traditional concept of Miller's pyramid (1990), demonstrated how CAPD novice turns skillful user by developing competence in cognition with factual knowledge of dialysis (‘Knows’) and verbalization of rationale and flows of PD (‘Knows How’); and competence in behavior with simulation practice with CAPD device (‘Shows’) and summative assessment demonstrating mastery of safe bag exchange skills to be integrated into everyday practice (‘Does’). Further studies may be warranted to investigate whether knowledge and skills acquired before use of CAPD could be carried over time and on how education program accounts for risk minimization of CAPD-related peritonitis and survival rate.

Microstructural alterations predict impaired bimanual control in Parkinson's disease.

Bimanual coordination is impaired in Parkinson’s disease affecting patients’ ability to perform activities of daily living and to maintain independence. Conveyance of information between cortical and subcortical areas is essential for bimanual coordination and relies on the integrity of cerebral microstructure. As pathological deposition of alpha-synuclein compromises microstructure in Parkinson’s disease, we investigated the relationship between microstructural integrity and bimanual coordination using diffusion-weighted MRI in 23 patients with Parkinson’s disease (mean age ± standard deviation: 56.0 ± 6.45 years; 8 female) and 26 older adults (mean age ± standard deviation: 58.5 ± 5.52 years). Whole-brain analysis revealed specific microstructural alterations between patients and healthy controls matched for age, sex, handedness, and cognitive status congruent with the literature and known Parkinson’s disease pathology. A general linear model revealed distinct microstructural alterations associated with poor bimanual coordination in Parkinson’s disease, corrected for multiple comparisons using a permutation-based approach. Integrating known functional topography, we conclude that distinct changes in microstructure cause an impediment of structures involved in attention, working memory, executive function, motor planning, motor control, and visual processing contributing to impaired bimanual coordination in Parkinson’s disease.

Experience in the application of remote anesthesia in Callorhinus ursinus

Marine mammals often become entangled in various objects of anthropogenic origin floating on the surface of the water. Plastic, polyethylene, synthetic packing straps, and fishing gear threaten marine mammals in the water and on land. The study was carried out on 29 specimens of Callorhinus ursinus. We used a combined Zoletil 100 and Medetin 1% for remote sedation of injured Callorhinus ursinus to release foreign objects.Resultsthe first signs of anesthesia were recorded 3‐5 minutes after drug delivery. The difficulty of movement, coordination disorder, weakness were noted. After 5‐15 minutes, the animals lay down but reacted to touch, and their eyes were open. After 15‐20 minutes, the animals lay motionless, practically not reacting to external stimuli. Their eyes were in a half‐closed state. In this state, it is possible to carry out manipulations to remove foreign objects from the animal. The depth of narcotic sleep varied depending on the dose: mild sedation developed at Medetin 1% 0.02‐0.03 mg/kg and Zoletil 100 0.45‐0.65 mg/kg. The animals were lying down, we could approach them, but they reacted to touches and loud sounds. The eyes were open, and it was dangerous to carry out any manipulations with such animals. The seals did not fall into a deep sleep; after 30‐60 minutes without the use of antagonists, they began to move, but there was a slight impairment of coordination of movements for 1‐2 hours. Moderate sedation was observed at a dose of 0.03‐0.05 mg / kg Medetin 1% and 0.5‐0.9 mg / kg Zoletil 100. The animals lay motionless; sometimes, there was a slight twitching of their fins, whiskers, or ears during manipulation of slight pain. Eyes half‐closed. It is possible to carry out small short‐term manipulations with the animal to remove a foreign object without strong painful sensations. After 30‐60 minutes, the seals wiggled their flippers and tried to raise their heads. They began to move independently after 1‐1.5 hours. Slight impairment of coordination was noted 1.5‐2 hours after full awakening. At a dose of 0.05‐0.09 mg/kg Medetin 1% and 0.8‐2.0 mg/kg Zoletil 100, the animals lay motionless and did not react to external stimuli, even during painful manipulations or movement. This sedation is deep, suitable for painful procedures to remove foreign objects with deep skin lesions. Without the use of antagonists, such animals woke up after 1‐1.5 hours. They began to move their flippers, mustache, move around after 2.5‐3 hours. Determining the optimal doses of drugs for remote anesthesia of marine mammals is essential, both for the safe release of foreign objects from the animals and also for the people who perform this work.

The INPP School Intervention programme in work with a student with specific learning difficulties by Sally Goddard Blythe

Changing the lifestyle to a more passive, less active one increases the threat to the development of the young generation. The phenomenon of physical inactivity is deteriorated by the ubiquitous computer, the Internet, and in the last two years by the pandemic and all kinds of restrictions. Numerous studies show that children diagnosed with impaired body coordination, balance and general mobility also experience failures in the learning process. It has been proven that methods based on physical activity support the education process with great success. The aim of the article is to present the general assumptions of the INPP School Intervention Programme by Sally Goddard Blythe as an effective form of supporting a student with specific school difficulties. The School Intervention Programme is successfully implemented in mainstream primary schools around the world.

Dietary restriction modulates mitochondrial DNA damage and oxylipin profile in aged rats.

Age-related impairment of coordination of the processes of maintaining mitochondrial homeostasis is associated with a decrease in the functionality of cells and leads to degenerative processes. mtDNA can be a marker of oxidative stress and tissue degeneration. However, the mechanism of accumulation of age-related damage in mtDNA remains unclear. In the present study, we analyzed the accumulation of mtDNA damage in several organs of rats during aging and the possibility of reversing these alterations by dietary restriction (DR). We showed that mtDNA of brain compartments (with the exception of the cerebellum), along with kidney mtDNA, was the most susceptible to accumulation of age-related damage, whereas liver, testis, and lung were the least susceptible organs. DR prevented age-related accumulation of mtDNA damage in the cortex and led to its decrease in the lung and testis. Changes in mtDNA copy number and expression of genes involved in the regulation of mitochondrial biogenesis and mitophagy were also tissue-specific. There was a tendency for an age-related decrease in the copy number of mtDNA in the striatum and its increase in the kidney. DR promoted an increase in the amount of mtDNA in the cerebellum and hippocampus. mtDNA damage may be associated not only with the metabolic activity of organs, but also with the lipid composition and activity of processes associated with the isoprostanes pathway of lipid peroxidation. The comparison of polyunsaturated fatty acids and oxylipin profiles in old rats showed that DR decreased the synthesis of arachidonic acid and its metabolites synthesized by the cyclooxygenase, cytochrome P450 monooxygenases and lipoxygenase metabolic pathways.

Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

Inflammasome Inhibition Prevents Motor Deficit and Cerebellar Degeneration Induced by Chronic Methamphetamine Administration

Methamphetamine (METH), a psychostimulant, has the potential to cause neurodegeneration by targeting the cerebrum and cerebellum. It has been suggested that the NLRP3 inflammasome may be responsible for the neurotoxicity caused by METH. However, the role of NLRP3 in METH-induced cerebellar Purkinje cell (PC) degeneration and the underlying mechanism remain elusive. This study aims to determine the consequences of NLRP3 modulation and the underlying mechanism of chronic METH-induced cerebellar PC degeneration. In METH mice models, increased NLRP3 expression, PC degeneration, myelin sheath destruction, axon degeneration, glial cell activation, and motor coordination impairment were observed. Using the NLRP3 inhibitor MCC950, we found that inhibiting NLRP3 alleviated the above-mentioned motor deficits and cerebellar pathologies. Furthermore, decreased mature IL-1β expression mediated by Caspase 1 in the cerebellum may be associated with the neuroprotective effects of NLRP3 inflammasome inhibition. Collectively, these findings suggest that mature IL-1β secretion mediated by NLRP3-ASC-Caspase 1 may be a critical step in METH-induced cerebellar degeneration and highlight the neuroprotective properties of inflammasome inhibition in cerebellar degeneration.

Appropriate Learning Methods for Autistic Children in Improving Tooth brushing Skills: a Review

Autistic children have poor oral hygiene levels higher than normal children. Dental and oral health problems that often occur in children with autism are the risk of dental caries which is higher than other dental and oral diseases. Frequent consumption of cariogenic foods and impaired coordination of the tongue muscles result in a tendency to eat food and difficulty swallowing, resulting in the formation of debris. The high value of debris causes calculus and if left further it will develop into worse tooth and gum damage. Objective: To describe appropriate learning methods for children with autism in improving their brushing skills. Methods: Search journals for 2016-2021 on Google Scholar, Pubmed, and Sciendirect databases. In the 8 journals used, 4 of them used quantitative research methods, 2 used prospective research methods, and 2 others used cross-sectional research methods. Results: The various methods obtained are the use of the PECS method; Yoga Therapy; iPads; Social Stories, TEACCH method, Puzzle Series; and Videos. Several kinds of learning methods are appropriate and can be recommended for children with autism, namely the video learning method which is considered better and can attract the attention of children with autism in improving their brushing skills.