CLINICAL APPLICATION OF BOTULINUM TOXIN TYPE B IN MOVEMENT DISORDERS AND AUTONOMIC SYMPTOMS

Objective To evaluate efficacy and safety of botulinum toxin type B (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular dystonia, hemifacial spasm, tremor, tics, and hypersecretory disorders such as sia-lorrhea and hyperhidrosis. Methods A retrospective study of BTX-B injections in treatment of 58 patients with various neurological disorders was performed. The mean follow-up time was 0.9 ± 0.8 years. Results of the first and last treatment of patients with at least 3 injection sessions were compared. Results The response of 58 patients to a total of 157 BTX-B treatment sessions was analyzed. Of the 157 treatment sessions, 120 sessions (76.4%) resulted in moderate or marked improvement while 17 sessions (10.8%) had no response. The clinical benefits after BTX-B treatment lasted an average of 14 weeks. Of the 41 patients with at least 3 injection ses-sions (mean 10 ± 8.6), most patients needed increased dosage upon the last session compared to the first session. Nineteen patients (32.8%) with 27 sessions (17.2%) reported adverse effects with BTX-B treatment. Conclusions Though most patients require increased dosage to maintain effective response after repeated injections, BTX-B is an effective and safe treatment drug for a variety of movement disorders, as well as drooling and hyperhidrosis.

Molecular imaging of movement disorders

Positron emission tomography measures the activity of radioactively labeled compounds which distribute and accumulate in central nervous system regions in proportion to their metabolic rate or blood flow. Specific circuits such as the dopaminergic nigrostriatal projection can be studied with ligands that bind to the pre-synaptic dopamine transporter or post-synaptic dopamine receptors (D1 and D2). Single photon emission computerized tomography (SPECT) measures the activity of similar tracers labeled with heavy radioactive species such as technetium and iodine. In essential tremor, there is cerebellar hypermetabolism and abnormal GABAergic function in premotor cortices, dentate nuclei and ventral thalami, without significant abnormalities in dopaminergic transmission. In Huntington’s disease, there is hypometabolism in the striatum, frontal and temporal cortices. Disease progression is accompanied by reduction in striatal D1 and D2 binding that correlates with trinucleotide repeat length, disease duration and severity. In dystonia, there is hypermetabolism in the basal ganglia, supplementary motor areas and cerebellum at rest. Thalamic and cerebellar hypermetabolism is seen during dystonic movements, which can be modulated by globus pallidus deep brain stimulation (DBS). Additionally, GABA-A receptor activity is reduced in motor, premotor and somatosensory cortices. In Tourette’s syndrome, there is hypermetabolism in premotor and sensorimotor cortices, as well as hypometabolism in the striatum, thalamus and limbic regions at rest. During tics, multiple areas related to cognitive, sensory and motor functions become hypermetabolic. Also, there is abnormal serotoninergic transmission in prefrontal cortices and bilateral thalami, as well as hyperactivity in the striatal dopaminergic system which can be modulated with thalamic DBS. In Parkinson’s disease (PD), there is asymmetric progressive decline in striatal dopaminergic tracer accumulation, which follows a caudal-to-rostral direction. Uptake declines prior to symptom presentation and progresses from contralateral to the most symptomatic side to bilateral, correlating with symptom severity. In progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), striatal activity is symmetrically and diffusely decreased. The caudal-to-rostral pattern is lost in PSP, but could be present in MSA. In corticobasal degeneration (CBD), there is asymmetric, diffuse reduction of striatal activity, contralateral to the most symptomatic side. Additionally, there is hypometabolism in contralateral parieto-occipital and frontal cortices in PD; bilateral putamen and cerebellum in MSA; caudate, thalamus, midbrain, mesial frontal and prefrontal cortices in PSP; and contralateral cortices in CBD. Finally, cardiac sympathetic SPECT signal is decreased in PD. The capacity of molecular imaging to provide in vivo time courses of gene expression, protein synthesis, receptor and transporter binding, could facilitate the development and evaluation of novel medical, surgical and genetic therapies in movement disorders.

Correlation study between motor rehabilitation level and psychological state in patients with limb movement disorders after stroke

BACKGROUND The psychological state of patients with post stroke limb movement disorders undergoes a series of changes that affect rehabilitation training and recovery of limb motor function.AIM To determine the correlation between motor rehabilitation and the psychological state of patients with limb movement disorders after stroke.METHODS Eighty patients with upper and lower limb dysfunction post stroke were retrospectively enrolled in our study.Based on Hospital Anxiety and Depression Scale(HADS)scores measured before rehabilitation,patients with HADS scores≥8 were divided into the psychological group;otherwise,the patients were included in the normal group.Motor function and daily living abilities were compared between the normal and psychological groups.Correlations between the motor function and psychological status of patients,and between daily living ability and psychological status of patients were analyzed.RESULTS After 1,2,and 3 wk of rehabilitation,both the Fugl-Meyer assessment and Barthel index scores improved compared to their respective baseline scores(P<0.05).A greater degree of improvement was observed in the normal group compared to the psychological group(P<0.05).There was a negative correlation between negative emotions and limb rehabilitation(-0.592≤r≤-0.233,P<0.05),and between negative emotions and daily living ability(-0.395≤r≤-0.199,P<0.05).CONCLUSION There is a strong correlation between motor rehabilitation and the psychological state of patients with post stroke limb movement disorders.The higher the negative emotions,the worse the rehabilitation effect.

Sleep-associated movement disorders and the risk of cardiovascular disease: A systematic review and metaanalysis

AIM:To investigate whether an association exists between sleep-associated movement disorders and cardiovascular disease(CVD).METHODS:Several studies have observed the relationship of sleep-associated movement disorders such as restless legs syndrome(RLS)and periodic limb movements during sleep with CVD,but the results were still contradictory.We performed an extensive literature search on Pub Med,Medline and Web of Science published from inception to December 2014.Additional studies were manually searched from bibliographies of retrieved studies.Meta-analyses were conducted with Stata version 12.0(Stata Corp,College Station,Texas).Pooled odds ratios(ORs)and 95%CIs were calculated to assess the strength of association using the random effects model.Sensitivity and subgroup analyses were performed to explore the underlying sources of heterogeneity.The publication bias was detected using Egger’s test and Begg’s test.RESULTS:A total of 781 unique citations were indentified from electronic databases and 13 articles in English were finally selected.Among these studies,nine are cohort studies;two are case-control studies;and two are cross-sectional studies.The results showed that the summary OR of CVD associated with sleepassociated movement was 1.51(95%CI:1.29-1.77)in a random-effects model.There was significant heterogeneity between individual studies(P for heterogeneity=0.005,I2=57.6%).Further analysis revealed that a large-scale cohort study may account for this heterogeneity.A significant association was also found between RLS and CVD(OR=1.54,95%CI:1.24-1.92).In a fixed-effects model,we determined a significant relationship between sleep-associatedmovement disorders and coronary artery disease(CAD)(OR=1.34,95%CI:1.16-1.54;P for heterogeneity=0.210;I2=30.0%).Our meta-analysis suggests that sleep-associated movement disorders are associated with prevalence of CVD and CAD.CONCLUSION:This finding indicates that sleep-associated movement disorders may prove to be predictive of underlying CVD.

Role of a wireless surface electromyography in dystonic gait in functional movement disorders: A case report

BACKGROUND Dystonic gait(DG) is one of clinical symptoms associated with functional dystonia in the functional movement disorders(FMDs). Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. There is no report for DG in FMDs caused by an abnormal pattern in the ankle muscle recruitment strategy during gait.CASE SUMMARY A 52-year-old male patient presented with persistent limping gait. When we requested him to do dorsiflexion and plantar flexion of his ankle in the standing and seating positions, we didn’t see any abnormality. However, we could see the DG during the gait. There were no evidences of common peroneal neuropathy and L5 radiculopathy in the electrodiagnostic study. Magnetic resonance imaging of the lumbar spine, lower leg, and brain had no definite finding. No specific finding was seen in the neurologic examination. For further evaluation, a wireless surface electromyography(EMG) was performed. During the gait, EMG amplitude of left medial and lateral gastrocnemius(GCM) muscles was larger than right medial and lateral GCM muscles. When we analyzed EMG signals for each muscle, there were EMG bursts of double-contraction in the left medial and lateral GCM muscles, while EMG analysis of right medial and lateral GCM muscles noted regular bursts of single contraction. We could find a cause of DG in FMDs.CONCLUSION We report an importance of a wireless surface EMG, in which other examination didn’t reveal the cause of DG in FMDs.

Transcranial sonography in differential diagnosis of Parkinson disease and other movement disorders

Background:Reports evaluating the efficacy of transcranial sonography(TCS)for the differential diagnosis of Parkinson disease(PD)and other movement disorders in China are scarce.Therefore,this study aimed to assess the application of TCS for the differential diagnosis of PD,multiple system atrophy(MSA),progressive supranuclear palsy(PSP),and essential tremor(ET)in Chinese individuals.Methods:From 2017 to 2019,500 inpatients treated at the Department of Dyskinesia,Beijing Tiantan Hospital,Capital Medical University underwent routine transcranial ultrasound examination.The cross-sections at the midbrain and thalamus levels were scanned,and the incidence rates of substantia nigra(SN)positivity and the incidence rates of lenticular hyperechoic area were recorded.The echo of the SN was manually measured.Results:Of the 500 patients,125 were excluded due to poor signal in temporal window sound transmission.Among the 375 individuals with good temporal window sound transmission,200 were diagnosed with PD,90 with ET,50 with MSA,and 35 with PSP.The incidence rates of SN positivity differed significantly among the four patient groups(χ^(2)=121.061,P<0.001).Between-group comparisons were performed,and the PD group showed a higher SN positivity rate than the ET(χ^(2)=94.898,P<0.017),MSA(χ^(2)=57.619,P<0.017),and PSP(χ^(2)=37.687,P<0.017)groups.SN positivity showed a good diagnostic value for differentiating PD from the other three movement diseases,collectively or individually.The incidences of lenticular hyperechoic area significantly differed among the four patient groups(χ^(2)=38.904,P<0.001).Next,between-group comparisons were performed.The lenticular hyperechoic area was higher in the PD group than in the ET(χ^(2)=6.714,P<0.017)and MSA(χ^(2)=18.680,P<0.017)groups but lower than that in the PSP group(χ^(2)=0.679,P>0.017).Conclusion:SN positivity could effectively differentiate PD from ET,PSP,and MSA in a Chinese population.

Implication of the LINGO2 gene in the predisposition to movement disorders

Previous reports on the pathogenesis of age-related movement disorders,such as Parkinson’s disease(PD)and essential tremor(ET),have demonstrated the potential implications of LINGO1(leucine-rich repeat and immunoglobulin domain-containing protein)gene.Although LINGO2 has a high degree of homology with LINGO1,but it is less characterized and the role of LINGO2 in the development of PD/ET remains unreported.Hence,this metaanalysis was conducted to evaluate the role of LINGO2 in PD/ET pathogenesis.A total of 4 studies,which complied with the Hardy-Weinberg equilibrium,were included in the meta-analysis.Analysis of the pooled odds ratio and confidence interval of the studies were performed for five genetic models,namely:allelic,dominant,recessive,homozygous,and heterozygous.No significant association was observed between the LINGO2 polymorphism and PD/ET,although subgroup analysis through conventional metaanalysis indicated that the recessive models of rs7033345 and rs10812774 are significantly associated with predisposition to ET in the Asian population.However,trial sequential analyses for both polymorphisms were unlikely to reveal any robust effect.Hence,studies with larger samples on this association are needed in the future to corroborate our results.

Botulinum Toxin Type A Satisfaction in Different Neurological Disorders

Background: The botulinum toxin type A (BoNT-A) is used in a wide range of neurological diseases. We aimed to study the overall patients/caregivers’ satisfaction with BoNT-A treatment in different neurological conditions. Methods: Prospective study included patients who had received at least two BoNT-A treatment sessions. They were asked to rate overall treatment satisfaction at the peak of treatment effect on a 1 to 10 scale (1 = not at all satisfied;10 = fully satisfied). Subjects with a rating of 1to3 were classified as not at all satisfied, those with a rating of 4 to7 as somewhat satisfied, and those with a rating of 8 to10 as very satisfied. Treatment satisfaction questionnaire for medicine (TSQM) was assessed at the end of observational period. Quality of life QOL was assessed before BoNT-A treatment and at the last visit. Results: The study was conducted from first April 2014 to August 2021. 548 patients were identified with mean age 43.66 ± 14.50. Most of participants 389 (71%) were female. At the end of observational period, the mean satisfaction was 7.28 ± 1.78. There was a highly significant difference (P P P = 0.001). Conclusion: Satisfaction with BoNT-A therapy for different neurological disorders is overall good. The highest patient satisfaction was observed with primary focal HH, and the least satisfaction was observed in writer’s cramp. BoNT-A therapy improved QOL.

Transient involuntary movement disorder after spinal anesthesia: A case report

BACKGROUND Spinal anesthesia is commonly used for various surgeries.While many complications occur after induction of spinal anesthesia,involuntary movement is an extremely rare complication.CASE SUMMARY Herein,we report the case of a 54-year-old healthy male patient who experienced involuntary movements after intrathecal injection of local anesthetics.This patient had undergone metal implant removal surgery in both the lower extremities;7 h after intrathecal hyperbaric bupivacaine administration,involuntary raising of the left leg began to occur every 2 min.When the movement disorder appeared,the patient was conscious and cooperative.No other specific symptoms were noted in the physical examination conducted immediately after the involuntary leg raising started;moreover,the patient's motor and sensory assessments were normal.The symptom gradually subsided.Twelve hours after the symptom first occurred,its frequency decreased to approximately once every three hours.Two days postoperatively,the symptoms had completely disappeared without intervention.CONCLUSION Anesthesiologists should be aware that movement disorders can occur after spinal anesthesia and be able to identify the cause,such as electrolyte imbalance or epilepsy,since immediate action may be required for treatment.Furthermore,it is crucial to know that involuntary movement that develop following spinal anesthesia is mostly self-limiting and may not require additional costly examinations.

Hemichorea in patients with temporal lobe infarcts: Two case reports

BACKGROUND Hemichorea and other hyperkinetic movement disorders are uncommon present-ations of stroke and are usually secondary to deep infarctions affecting the basal ganglia and thalamus.Therefore,temporal ischemic lesions causing hemichorea are rare.We report the cases of two patients with acute ischemic temporal lobe infarct strokes that presented as hemichorea.CASE SUMMARY Patient 1:An 82-year-old woman presented with a 1-mo history of involuntary movement of the left extremity,which was consistent with hemichorea.Her diffusion-weighted imaging(DWI)revealed an acute ischemic stroke that predominantly affected the right temporal cortex,and magnetic resonance angiography of the head showed significant stenosis of the right middle cerebral artery(MCA).Treatment with 2.5 mg of olanzapine per day was initiated.When she was discharged from the hospital,her symptoms appeared to have improved compared with those previously observed.Twenty-seven days after the first admission,she was readmitted due to acute ischemic stroke.Computed tomogra-phy perfusion showed marked hypoperfusion in the right MCA territory.An emergency transfemoral cerebral angiogram was performed and showed severe stenosis in the M1 segment of the right MCA.After percutaneous transluminal angioplasty was successfully performed,abnormal movements or other neuro-logic problems did not occur.Patient 2:A 76-year-old man was admitted to our hospital for a 7-d history of right-upper-sided involuntary movements.DWI showed an acute patchy ischemic stroke in the left temporal lobe without basal ganglia involvement.Subsequent diffusion tensor imaging confirmed fewer white matter fiber tracts on the left side than on the opposite side.Treatment with 2.5 mg of olanzapine per day improved his condition,and he was discharged.CONCLUSION When acute hemichorea suddenly appears,temporal cortical ischemic stroke should be considered a possible diagnosis.In addition,hemichorea may be a sign of impending cerebral infarction with MCA stenosis.

Transcranial Direct Current Stimulation: Effects on Motor and Non-Motor Symptoms of Parkinson’s Disease

Introduction: In the last thirty years, brain neuromodulation techniques have been used as an alternative to pharmacological treatment of neurological disorders. Parkinson’s disease (PD) is a neurodegenerative disorder leading to bradykinesia, rest tremor, postural changes, and non-motor symptoms such as depression, anxiety, sleep disorders, pain, and cognitive decline that compromises executive functions (EFs), responsible for the orderly execution of behaviors and tasks of daily life and intentional and directed actions. To this date, a few studies with transcranial direct current stimulation (tDCS) have shown beneficial effects in PD patients concerning specific motor and non-motor symptoms, targeting the motor cortex and/or prefrontal regions. Objective: The main objective of this study was to evaluate the effects of left prefrontal tDCS across a broad spectrum of motor and non-motor symptoms of PD using established validated scales. Method: Single-blind randomized clinical trial with 18 volunteers with PD, aged between 45 and 80 years (66.1 ± 9.65), who met inclusion and exclusion criteria. Participants were submitted to assessments of motor and non-motor functions employing psychometric scales and tests to evaluate EFs and were randomly divided into two groups: control (sham stimulation) and experimental (active stimulation). All participants were involved in three separate tDCS sessions. The anode was positioned over the left dorsolateral prefrontal cortex and the cathode over the right supraorbital region, with a direct current intensity of 2 mA, lasting 20 minutes. At the end of the three sessions, all participants were reassessed. Results: Significant effects of tDCS on non-motor functions were observed for cognition (verbal fluency of actions, clock copy test, appointment by visual confrontation, and verbal memory with immediate free recall) and subjective assessment of sleep quality (overall restlessness and discomfort in the arms and legs at night, leg and arm cramps at night and distressing dreams). There was also an improvement in the rate of errors and successes for congruent and incongruent stimuli of the Stroop Test. The beneficial effects on motor function were decreased rigidity, improved gait, and greater agility in the finger-tapping test. Conclusion: Three tDCS sessions showed positive results for participants with PD, producing significant improvements in various motor and non-motor functions, including sleep quality, cognition, and EFs. Additionally, the present results indicate that tDCS neuromodulation of the left dorsolateral prefrontal cortex region is feasible, safe, and provides significant objective benefits for PD patients.

Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

Rare coexistence of multiple manifestations secondary to thalamic hemorrhage:A case report

BACKGROUND A growing body of literature indicates that the occurrence of thalamic lesions could lead to various dysfunctions,such as somatosensory disturbances,hemiparesis,language deficits,and movement disorders.However,clinical cases describing the coexistence of these types of manifestations have not been reported.Herein,we report a patient who exhibited these rare complications secondary to thalamic hemorrhage.CASE SUMMARY A 53-year-old right-handed man experienced sudden left hemiparesis,numbness of the left side of body,and language alterations due to an acute hemorrhage located in the right basal ganglia and thalamus 18 mo ago.Approximately 17 mo after the onset of stroke,he exhibited rare complications including dysphasia,kinetic tremor confined to the left calf,and mirror movement of the left arm which are unique and interesting,and a follow-up computed tomography scan revealed an old hemorrhagic lesion in the right thalamus and posterior limb of the internal capsule.CONCLUSION Hypophonia may be a recognizable clinical sign of thalamus lesions;thalamus injury could cause tremor confined to the lower extremity and mimicking extremity movements.

Is tremor related to celiac disease?

Neurological features in celiac disease(CD) are not rare(5%-36%), but tremor is scarcely described. Subjects with CD and healthy controls completed an online survey using WHIGET tremor rating scale. One thousand five hundred and twelve subjects completed the survey, finally 674 CD patients and 290 healthy subjects were included. A higher prevalence of tremor in CD patients was observed in comparison to controls(28% vs 14%, P < 0.001). Frequency of family history of tremor in CD patients with and without tremor was 25% and 20%(P = 0.2), while in the control group it was 41% and 10%(P < 0.001). Controls with tremor showed a higher frequency of family history of tremor when compared to CD patients with tremor(41.5% vs 24.6%, P = 0.03). The results suggested that tremor in CD might be more frequent and possibly related to the disease itself and not due to associated essential tremor.

Validity and reliability of the Ocular Motor Nerve Palsy Scale

Objective and accurate assessment of the degree of ocular motor nerve palsy is helpful not only in the evaluation of prognosis, but also for the screening of treatment methods. However, there is currently no comprehensive measure of its severity. In this study, we designed the Ocular Motor Nerve Palsy Scale and investigated its validity and reliability. Six experts were invited to grade and evaluate the scale. The study recruited 106 patients with a definite diagnosis of unilateral isolated ocular motor nerve palsy. Three physicians evaluated the patients using the scale. One of the three physicians evaluated the patients again after 24 hours. The content validity index（CVI） and factor analysis were used to analyze the scale＇s construct validity. The intraclass correlation coefficient and Cronbach＇s alpha were used to evaluate the inter-rater and test-retest reliability and the internal consistency. The CVI results（I-CVI = 1.0, S-CVI = 0.9, Pc = 0.016, K＊ = 1） indicated good content validity. Factor analysis extracted two common factors that accounted for 85.2% of the variance. Furthermore, the load value of each component was above 0.8, indicating good construct validity. The Ocular Motor Nerve Palsy Scale was found to be highly reliable, with an inter-rater reliability intraclass correlation coefficient of 0.965（P 0.01）, a test-retest reliability intraclass correlation coefficient of 0.976（P 0.01）, and Cronbach＇s alpha values of 0.63–0.70. In conclusion, the Ocular Motor Nerve Palsy Scale with good validity and reliability can be used to quantify the severity of ocular motor nerve palsy. This study was registered at Chinese Clinical Trial Registry（registration number： Chi CTR-OOC-17010702）.

Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor

Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

Development of a depression in Parkinson's disease prediction model using machine learning

BACKGROUND It is important to diagnose depression in Parkinson’s disease(DPD)as soon as possible and identify the predictors of depression to improve quality of life in Parkinson’s disease(PD)patients.AIM To develop a model for predicting DPD based on the support vector machine,while considering sociodemographic factors,health habits,Parkinson's symptoms,sleep behavior disorders,and neuropsychiatric indicators as predictors and provide baseline data for identifying DPD.METHODS This study analyzed 223 of 335 patients who were 60 years or older with PD.Depression was measured using the 30 items of the Geriatric Depression Scale,and the explanatory variables included PD-related motor signs,rapid eye movement sleep behavior disorders,and neuropsychological tests.The support vector machine was used to develop a DPD prediction model.RESULTS When the effects of PD motor symptoms were compared using“functional weight”,late motor complications(occurrence of levodopa-induced dyskinesia)were the most influential risk factors for Parkinson's symptoms.CONCLUSION It is necessary to develop customized screening tests that can detect DPD in the early stage and continuously monitor high-risk groups based on the factors related to DPD derived from this predictive model in order to maintain the emotional health of PD patients.

Apelin-13 regulates electrical activity in the globus pallidus and induces postural changes in rats

The globus pallidus is the relay nucleus of the basal ganglia,and changes in its electrical activity can cause motor impairment.Apelin-13 is widely distributed in the central and peripheral nervous systems.It has been demonstrated that apelin-13 plays important roles in the regulation of blood pressure and other non-motor functions.However,its role in motor function has rarely been reported.In the present study,apelin-13(10μM/100μM)was injected into the globus pallidus of rats.The results showed that apelin-13 increased the spontaneous discharges in the majority of pallidal neurons.However,an apelin-13-induced inhibitory effect on the firing rate was also observed in a few pallidal neurons.In postural tests,after the systemic administration of haloperidol,unilateral pallidal injection of apelin-13 caused a contralateral deflection.Together,these findings suggest that apelin-13 regulates the electrical activity of pallidal neurons and thus participates in central motor control in rats.The study was approved by the Animal Ethics Committee of Qingdao University(approval No.20200615Wistar0451003020)on June 15,2020.

Sleep Disturbance in Parkinson’s Disease Varies with Age of Onset and Family History

Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-motor symptoms. Sleep disturbances, such as rapid eye movement (REM) behavior disorder (RBD), are common in patients with PD and may precede onset of PD. Methods: Data was collected on patients with PD (358 subjects)in a movement disorders clinic at a safety net hospital. In this retrospective database analysis, the association of PD complications with age of onset was evaluated using chi-square tests and logistic regression. Results: Of the PD complications analyzed, there was a significant difference in sleep disturbances by age. Among the 358 PD patients, 120 individuals (33.5%) had information regarding the presence or absence of sleep disturbances. There was a significant difference between the early (onset < 50) and later onset (≥50) groups (p = 0.03) with the odds of having a sleep disorder for the early group 1.6 times that of the late group. Those subjects with siblings who also had PD had 2.0 times the odds of having a sleep disorder compared those without (p = 0.02). Conclusion: Non-motor symptoms such as sleep disorders are a useful predictor of early onset PD. Genetic components of PD impact both motor and non-motor aspects of the disease.