Movement Disorders In Children Research Articles

Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

3D gait analysis in children using wearable sensors: feasibility of predicting joint kinematics and kinetics with personalized machine learning models and inertial measurement units.

Introduction: Children's walking patterns evolve with age, exhibiting less repetitiveness at a young age and more variability than adults. Three-dimensional gait analysis (3DGA) is crucial for understanding and treating lower limb movement disorders in children, traditionally performed using Optical Motion Capture (OMC). Inertial Measurement Units (IMUs) offer a cost-effective alternative to OMC, although challenges like drift errors persist. Machine learning (ML) models can mitigate these issues in adults, prompting an investigation into their applicability to a heterogeneous pediatric population. This study aimed at 1) quantifying personalized and generalized ML models' performance for predicting gait time series in typically developed (TD) children using IMUs data, 2) Comparing random forest (RF) and convolutional neural networks (CNN) models' performance, 3) Finding the optimal number of IMUs required for accurate predictions. Methodology: Seventeen TD children, aged 6 to 15, participated in data collection involving OMC, force plates, and IMU sensors. Joint kinematics and kinetics (targets) were computed from OMC and force plates' data using OpenSim. Tsfresh, a Python package, extracted features from raw IMU data. Each target's ten most important features were input in the development of personalized and generalized RF and CNN models. This procedure was initially conducted with 7 IMUs placed on all lower limb segments and then performed using only two IMUs on the feet. Results: Findings suggested that the RF and CNN models demonstrated comparable performance. RF predicted joint kinematics with a 9.5% and 19.9% NRMSE for personalized and generalized models, respectively, and joint kinetics with an NRMSE of 10.7% for personalized and 15.2% for generalized models in TD children. Personalized models provided accurate estimations from IMU data in children, while generalized models lacked accuracy due to the limited dataset. Furthermore, reducing the number of IMUs from 7 to 2 did not affect the results, and the performance remained consistent. Discussion: This study proposed a promising personalized approach for gait time series prediction in children, involving an RF model and two IMUs on the feet.

Whole Genome Expression Profiling of Semitendinosus Tendons from Children with Diplegic and Tetraplegic Cerebral Palsy.

Cerebral palsy (CP) is the most common movement disorder in children, with a prevalence ranging from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraplegic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased expression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetraplegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways, similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Nevertheless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

Analysis of movement disorders in paediatric and adolescent rheumatology

Rheumatic diseases in childhood and adolescence like juvenile idiopathic arthritis can cause movement disorders due to pain, swelling and limited range of motion. This article describes different possibilities and results of movement analysis for rheumatic diseases. The influence of JIA on specific movements in individual joints and complex movements such as gait is examined. The results of gait analyses show agreat influence of the disease on spatiotemporal parameters such as gait speed, cadence and stride length, on joint angles during walking and on torques and forces. Furthermore, the importance of gait analysis for estimating the efficacy of interventions like intra-articular steroids is described. This article provides asummary of current studies on the effects of rheumatic diseases on movement disorders in children and adolescents, as well as an outlook on the increasing importance of movement analysis for therapy monitoring and optimisation.

Dopamine Transporter Deficiency Syndrome (DTDS): Expanding the Clinical Phenotype and Precision Medicine Approaches.

Infantile parkinsonism-dystonia due to dopamine transporter deficiency syndrome (DTDS) is an ultrarare childhood movement disorder caused by biallelic loss-of-function mutations in the SLC6A3 gene. Advances in genomic analysis have revealed an evolving spectrum of SLC6A3-related neurological and neuropsychiatric disorders. Since the initial clinical and genetic characterisation of DTDS in 2009, there have been thirty-one published cases with a variety of protein-truncating variants (nonsense variants, splice-site changes, and deletions) and missense changes. Amino acid substitutions result in mutant proteins with impaired dopamine transporter function due to reduced transporter activity, impaired dopamine binding, reduced cell-surface expression, and aberrant posttranslational protein modification with impaired glycosylation. In this review, we provide an overview of the expanding clinical phenotype of DTDS and the precision therapies in development, including pharmacochaperones and gene therapy.

0705 Restless sleep disorder and periodic limb movement disorder in children with history of prematurity

Abstract Introduction Children with history of prematurity are at higher risk of complications, comorbidities and iron deficiency, including restless legs syndrome and periodic limb movements of sleep (PLMS). In this study we assess the prevalence of restless sleep disorder and PLMS in children with history of prematurity. Methods Retrospective chart review of sleep studies in children aged 1-18 years, with history of prematurity, from July 2021 to July 2022 at Seattle Children's Hospital. Only diagnostic studies in children without diagnosis of a genetic syndrome or airway surgery were included. Results During the study, 2,577 sleep studies were conducted, 162 were in children with history of prematurity (6%): 25 were split or titration studies (14%), 29 children had syndromes (Down, Prader Willi, Wiedmann Beckmann, Achondroplasia), 4 tracheostomy studies, 6 in infants aged < 12 months and 6 were post airway intervention. Ninety-two diagnostic studies were included in analysis. Median birth age was 31 weeks, interquartile range (IQR) 27-34 weeks. Thirty-two (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring; 18% had PLMS index >5/hour, 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters between the children with RSD, PLMS and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p=0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5), or than in the nonRSD/nonPLMS group (median 2.0, IQR 0.8-4.5). Altogether, children with RSD and those with PLMS had restless sleep as an indication for the sleep study in 70% of cases while snoring was the indication in only 26.7% of them. Conclusion We have previously reported that in the Seattle Children's Hospital Sleep Center the prevalence of RSD is 7.7% and that of PLMS is 9.3%; in this new analysis we found a higher frequency of RSD and elevated PLMS in children with history of prematurity. Premature children are higher risk of iron deficiency, among other complications and comorbidities. These new results confirm the previous reports of increased PLMS and add new knowledge on the prevalence of RSD in these children Support (if any)

Sleep-related rhythmic movement disorder in children: a mini-review.

Sleep-related rhythmic movement disorder (SRRMD) occurs in both infants and children. This disorder rarely occurs or persists in adolescence or adulthood. Rhythmic movement during sleep in children is often asymptomatic and considered a benign condition. It is classified as SRRMD when movement significantly disrupts sleep, results in daytime functional impairment, or causes self-inflicted body injury. Several studies have demonstrated that SRRMD occurs in all sleep stages. Few studies have investigated rhythmic movement disorder (RMD) in children. SRRMD is a clinical diagnosis supported by home video recordings. When the clinical history is insufficient to provide a definitive diagnosis of SRRMD, and other sleep-related conditions or seizure disorders are suspected, video-polysomnography is indicated. There are currently no clinical guidelines for treating SRRMD.

A clinical case of a developmental disorder of the nervous system with involuntary movements associated with the spectrum of GNAO1-associated diseases

Nervous Developmental Disorder with Involuntary Movements (NEDIM) (OMIM 617493) is a rare movement disorder in children on the spectrum of GNAO1-associated movement disorders. With NEDIM, movement disorders appear in early childhood, progress and lead to disability. The disease is caused by pathogenic heterozygous variants in the GNAO1 gene and has an autosomal dominant mode of inheritance. The epidemiology of NEDIM has not yet been established. Clinical symptoms are extensive, ranging from severe motor and cognitive impairment with self-injurious behaviour and seizures to a mild phenotype of movement disorders without mental retardation and seizures. Some patients develop epilepsy. Hyperkinetic syndrome in most children is manifested with chorea, athetosis, dystonia, and ballism, affecting the muscles of the body, limbs and face. According to MRI, in some patients, gradually progressive atrophy of the brain substance is visualized. Currently, the disease has no developed pathogenetic methods of therapy. Treatment is symptomatic, including various drug regimens to reduce the severity of movement disorders and seizures. Management of nutrition of the patient and the prevention of secondary complications of movement disorders are also important. In foreign sources there is described the experience of using topiramate and teterabenazine, as well as deep brain stimulation (DBS), which demonstrate a good effect in the form of a significant reduction in the frequency of dystonic storms and the severity of motor disorders. The article presents a clinical case of diagnosis and treatment of a child with this disease, and also current trends in therapy.

Behavioural sleep problems in children.

Behavioural sleep problems are very common in children and are concerns for many parents. This review discusses normal sleep physiology and sleep development and focuses on common behavioural sleep problems in childhood, including behavioural insomnia of childhood, parasomnias and sleep-related movement disorders, highlighting their clinical features and management. Behavioural insomnia of childhood is characterised by learned difficulties in falling asleep and/or staying asleep. Management includes establishing bedtime routines and behavioural techniques. Parasomnias include confusional arousals, sleepwalking, sleep terrors and nightmares, and these usually resolve with time. Management includes parental reassurance and behavioural interventions such as scheduled awakening. With regards to sleep enuresis, management includes behavioural modifications, enuresis alarm and desmopressin. Sleep-related movement disorders include sleep-related bruxism and sleep-related rhythmic movements, of which body rocking is the most common. Early identification and management of behavioural sleep problems may prevent their negative impact on children as well as their families.

Opsoclonus Myoclonus Syndrome and Supraventricular Tachycardia in a Pediatric Patient: A Case Report and Literature Review

Objective NA. Background Opsoclonus myoclonus syndrome (OMS) is a rare movement disorder in children often associated with an underlying neuroblastoma. In other cases, it is believed that the tumor is occult or there is another immune-stimulating precipitating event. Diagnosis can be difficult, requiring 3 of 4 criteria: opsoclonus or ocular flutter, myoclonus or ataxia, behavioral or sleep disturbances, and neuroblastoma. Prompt treatment of OMS is crucial to preventing permanent neurologic sequelae. In order to better characterize the clinical profile of this syndrome and its associated conditions, we present a case report of a 9 month old male with OMAS without an associated neuroblastoma and with new onset supraventricular tachycardia (SVT) and review the associated literature. Design/Methods NA. Results A 9-month-old male with a past medical history of macrocephaly, hypotonia, and developmental delay presented with abnormal eye and body movements starting one month prior. Due to concern for OMS, the patient underwent an extensive initial workup including CT neck, chest, abdomen, and pelvis and VHA/HMA levels, which were all within normal limits. The patient's spinal fluid revealed no evidence of paraneoplastic, autoimmune, or infectious processes. Per neurology recommendations, the patient was started on IVIG and dexamethasone. After his first IVIG infusion, the patient's abnormal movements worsened, and his heart rate increased into the 300s. The IVIG was discontinued. However, the patient continued to have recurring bouts of SVT, which was eventually controlled with digoxin. After resuming treatment with IVIG and dexamethasone, the patient's opsoclonus myoclonus symptoms began to improve. All additional metabolic labs resulted normal and the patient was discharged. Conclusions Because OMS can cause permanent developmental delay, prompt recognition and treatment of this syndrome is necessary. This is a unique case of OMAS without neuroblastoma, associated with recurrent bouts of SVT. Recognizing rare complications of OMS is crucial to improving medical management of its sequelae.

Translating Genetic Discovery into a Mechanistic Understanding of Pediatric Movement Disorders: Lessons from Genetic Dystonias and Related Disorders.

The era of next-generation sequencing has increased the pace of gene discovery in the field of pediatric movement disorders. Following the identification of novel disease-causing genes, several studies have aimed to link the molecular and clinical aspects of these disorders. This perspective presents the developing stories of several childhood-onset movement disorders, including paroxysmal kinesigenic dyskinesia, myoclonus-dystonia syndrome, and other monogenic dystonias. These stories illustrate how gene discovery helps focus the research efforts of scientists trying to understand the mechanisms of disease. The genetic diagnosis of these clinical syndromes also helps clarify the associated phenotypic spectra and aids the search for additional disease-causing genes. Collectively, the findings of previous studies have led to increased recognition of the role of the cerebellum in the physiology and pathophysiology of motor control-a common theme in many pediatric movement disorders. To fully exploit the genetic information garnered in the clinical and research arenas, it is crucial that corresponding multi-omics analyses and functional studies also be performed at scale. Hopefully, these integrated efforts will provide us with a more comprehensive understanding of the genetic and neurobiological bases of movement disorders in childhood.

Childhood movement disorders: Clinicoetiological pattern and long-term follow-up at tertiary care center from South India.

Movement disorders are common neurological problems. There is a considerable delay in the diagnosis of movement disorders which indirectly indicates their under-recognition. The studies regarding relative frequencies and their underlying etiology are limited. Describing and classifying them with a diagnosis helps in treating the condition. To study the clinical pattern of various movement disorders in children and to establish their etiology and outcome. This observational study was conducted in tertiary care hospital from January 2018 to June 2019. Children from 2 mo. to 18 years of age presenting with involuntary movements on the first Monday of every week were included in the study. History and clinical examination were carried out with a pre-designed proforma. A diagnostic workup was done, results were analyzed to find the common movement disorders and their etiology, and follow-up was analyzed for 3 years. A total of 100 cases out of 158 with known etiology were included in the study of which 52% were females and 48% were males. The mean age at presentation was 3.15 years. The various movement disorders are dystonia-39(39%), choreoathetosis-29(29%), tremors-22(22%), gratification reaction-7(7%), and shuddering attacks-4(4%). Ballismus and myoclonus were found in 3(3%) children each. Tics, stereotypes, and hypokinesia were found in 2(2%) children each. A total of 113 movement disorders were found in 100 children. Etiologically, perinatal insult was the most common cause 27(27%), followed by metabolic/genetic/hereditary causes 25(25%). Infantile tremor syndrome due to Vitamin B12 deficiency-16/22(73%), was a major contributor in children with tremors. Rheumatic chorea was less in our study 5(5%). Out of the 100 study subjects, 72 cases were followed up. Out of which 26 children have completely recovered. Based on the modified Rankins score(MRS), 7 children belong to category I, 2 children belong to category II, 1 child to category III, 6 children to category IV, and 14 children to category V of MRS. A total of 16 children have died (MRS VI). Perinatal insult and Infantile tremor syndrome are more important and preventable causes. Rheumatic chorea is found to be less common. A significant number of children had more than one type of movement disorder, which warrants the need to look for varied types of movement disorders in the same child. Long-term follow-up shows complete recovery in one-fourth of children and the remaining surviving with disability.

Diagnosing Common Movement Disorders in Children.

This article is designed to help the clinician identify the most common pediatric movement disorders and recognize benign versus pathologic movements in infancy and childhood, with a particular focus on treatable conditions and those that should not be missed. As telehealth has become more prevalent as a means of providing health care services, the challenges of obtaining relevant examination findings during telehealth encounters for assessment of children with movement disorders have become evident. Although many children who present with a chief complaint of "abnormal movements" are found to have a benign, self-resolving etiology, it is critical that neurologists accurately recognize benign versus pathologic movements in children to ensure appropriate diagnosis and intervention.

A Novel Missense Mutation in ERCC8 Co-Segregates with Cerebellar Ataxia in a Consanguineous Pakistani Family.

Autosomal-recessive cerebellar ataxias (ARCAs) are heterogeneous rare disorders mainly affecting the cerebellum and manifest as movement disorders in children and young adults. To date, ARCA causing mutations have been identified in nearly 100 genes; however, they account for less than 50% of all cases. We studied a multiplex, consanguineous Pakistani family presenting with a slowly progressive gait ataxia, body imbalance, and dysarthria. Cerebellar atrophy was identified by magnetic resonance imaging of brain. Using whole exome sequencing, a novel homozygous missense mutation ERCC8:c.176T>C (p.M59T) was identified that co-segregated with the disease. Previous studies have identified homozygous mutations in ERCC8 as causal for Cockayne Syndrome type A (CSA), a UV light-sensitive syndrome, and several ARCAs. ERCC8 plays critical roles in the nucleotide excision repair complex. The p.M59T, a substitution mutation, is located in a highly conserved WD1 beta-transducin repeat motif. In silico modeling showed that the structure of this protein is significantly affected by the p.M59T mutation, likely impairing complex formation and protein-protein interactions. In cultured cells, the p.M59T mutation significantly lowered protein stability compared to wildtype ERCC8 protein. These findings expand the role of ERCC8 mutations in ARCAs and indicate that ERCC8-related mutations should be considered in the differential diagnosis of ARCAs.

Intravenous iron therapy alleviates symptoms of sleep-related movement disorders in children with minimal side effects.

Intravenous iron therapy alleviates symptoms of sleep-related movement disorders in children with minimal side effects.

Childhood-Onset Intractable Neurological Disorders, Mainly Movement Disorders

Some intractable neurological disorders, mainly movement disorders of childhood, have been outlined. It is recommended that healthcare transition be provided in a multidisciplinary setting to meet patient needs. The pediatrician in charge of transitional patients should take the lead in providing advice on the advantages and disadvantages of medical options, while respecting the patient's and family/guardian's right to self-determination to jointly reach a satisfactory decision. Here, we briefly described some of the issues that cause transition difficulties.

An overview of the effects of whole-body vibration on individuals with cerebral palsy

The purpose of this review is to examine how whole-body vibration can be used as a tool in therapy to help improve common physical weaknesses in balance, bone density, gait, spasticity, and strength experienced by individuals with cerebral palsy. Cerebral palsy is the most common movement disorder in children, and whole-body vibration is quickly becoming a potential therapeutic tool with some advantages compared to traditional therapies for individuals with movement disorders. The advantages of whole-body vibration include less strain and risk of injury, more passive training activity, and reduced time to complete an effective therapeutic session, all of which are appealing for populations with physiological impairments that cause physical weakness, including individuals with cerebral palsy. This review involves a brief overview of cerebral palsy, whole-body vibration's influence on physical performance measures, its influence on physical performance in individuals with cerebral palsy, and then discusses the future directions of whole-body vibration therapy in the cerebral palsy population.

Altered gene expression levels of genes related to muscle function in adults with cerebral palsy

Cerebral palsy (CP) is the most common cause of movement disorders in children. Next generation sequencing (NGS) studies have previously shown that expression levels are fundamentally different in children with CP compared to typically developing (TD). However, given that children are in full development, we might expect gene expression levels to change once maturity is reached. Therefore, the main purpose of this study was to investigate gene expression levels of 93 target genes in adults with CP using NGS on muscle biopsies of the gastrocnemius, taken from 22 participants (n = 12 adults with CP; n = 10 TD adults). Subsequently, we carried out NGS of the mitochondrial genome to identify mtDNA variants, and additionally we studied the mitochondrial content using transmission electron microscopy images of the gastrocnemius muscle. Finally, we compared systemic ion levels between TD adults and adults with CP. Differential gene expression levels were found in genes involved in muscle contraction (MYH1 and MYBPC2), mitochondrial function kATP5J, CYCS and NDUFB6), calcium handling (CAMK2B and ATP2A), metabolism (LPL), muscle signaling (MYC, CREB1, ACVR2B, LMNA and TRIM54), and ECM (TNC). There was no statistical significant difference between CP and TD for mtDNA variant frequencies and mitochondrial content. The ion levels of Ca2+, Na+ and K+ were statistically significantly reduced while the Cl− levels were significant increased in adults with CP compared to TD adults. These results highlight that most transcriptional differences are related to muscle function in adults with CP and that mitochondrial function might be altered but not mitochondrial content.

Movement disorders, cerebral palsy and vaccination.

This review focused on vaccination in children with movement disorders, including cerebral palsy and the movement disorders triggered by vaccination in children with and without neurological disabilities. The following clinical questions were addressed: 1) Can children with movement disorders be vaccinated? 2) Can vaccination trigger movement disorders in children without neurological disabilities? 3) Can vaccination trigger movement disorders in children with neurological disabilities? and 4) Is there any consensus of care concerning vaccination in children with movement disorders? Following the PRISMA reporting guidelines, 1096 records were identified and 34 relevant papers were included. No evidence that vaccinations are contraindicated for children with movement disorders was noticed. Several reports of neurological adverse events, including movement disorders in children without neurological disabilities after various types of vaccination, were found. The reporting rates were low, the causality was controversial, and patient outcomes were mostly favourable. There was limited (if any) evidence in our search that any vaccination leads to any movement disorder exacerbation. Finally, no generally accepted consensus or standards of care concerning vaccination in patients with movement disorders were found. In summary, we found few precautions for vaccination in this group of patients and concluded that general best practice guidelines for immunization should be followed. In addition, influenza and pneumococcal vaccines are recommended because they can reduce morbidity and mortality in individuals severely affected by movement restrictions.

Medication Error : Haloperidol Toxicity In A Child With Intellectual Disability

Haloperidol is a typical antipsychotic drug used in the treatment of schizophrenia and mania in adults, and for hyperactivity, behavioural and movement disorders in children. A common adverse effect of this drug is the development of extrapyramidal symptoms due to the blockage of dopamine receptors. Here we report a case of haloperidol toxicity due to medication error.