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Experimental and Clinical Endocrinology... Jun 2020Despite its first description more than 75 years ago, effective treatment for "Allan-Herndon-Dudley-Syndrome (AHDS)", an X-linked thyroid hormone transporter defect, is... (Review)
Review
Despite its first description more than 75 years ago, effective treatment for "Allan-Herndon-Dudley-Syndrome (AHDS)", an X-linked thyroid hormone transporter defect, is unavailable. Mutations in the gene have been discovered to be causative for AHDS in 2004, but a comprehensive understanding of the function of the encoded protein, monocarboxylate transporter 8 (MCT8), is incomplete. Patients with AHDS suffer from neurodevelopmental delay, as well as extrapyramidal (dystonia, chorea, athetosis), pyramidal (spasticity), and cerebellar symptoms (ataxia). This suggests an affection of the pyramidal tracts, basal ganglia, and , most likely already during fetal brain development. The function of other brain areas relevant for mood, behavior, and vigilance seems to be intact. An optimal treatment strategy should thus aim to deliver T3 to these relevant structures at the correct time points during development. A potential therapeutic strategy meeting these needs might be the delivery of T3 a "Trojan horse mechanism" by which T3 is delivered into target cells by a thyroid hormone transporter independent T3 internalization.
Topics: Basal Ganglia; Cerebellum; Humans; Mental Retardation, X-Linked; Monocarboxylic Acid Transporters; Muscle Hypotonia; Muscular Atrophy; Pyramidal Tracts; Triiodothyronine
PubMed: 32242326
DOI: 10.1055/a-1108-1456 -
Seminars in Fetal & Neonatal Medicine Feb 2015Bilirubin-induced neurologic dysfunction (BIND) is a syndrome of subtle bilirubin neurotoxic disorders. The risk for developing BIND in newborns usually increases with... (Review)
Review
Bilirubin-induced neurologic dysfunction (BIND) is a syndrome of subtle bilirubin neurotoxic disorders. The risk for developing BIND in newborns usually increases with elevated serum/plasma concentrations of unconjugated bilirubin. This risk is further increased by disorders of bilirubin binding to albumin, which includes a reduction in serum albumin concentrations or in the bilirubin-binding capacity and affinity of albumin, and the presence of displacing substances or infection. Serum unbound bilirubin (UB) concentration may be an ideal marker that reflects changes in bilirubin binding to albumin. Kernicterus, the chronic and with the most severe manifestations beyond BIND, is diagnosed by the presence of motor impairments with athetosis, abnormal magnetic resonance imaging, and/or brainstem auditory-evoked potential findings during infancy and childhood. Preterm infants sometimes have acute bilirubin encephalopathy without marked hyperbilirubinemia, such that bilirubin neurotoxicity occurs at bilirubin thresholds lower than usually associated with kernicterus. Disorders of bilirubin binding to albumin may be associated with the clinical signs of neurological injury associated with the lower bilirubin levels observed in preterm infants.
PubMed: 25432488
DOI: 10.1016/j.siny.2014.11.001 -
Neuropediatrics Oct 2021Paroxysmal dyskinesias (PD) are rare movement disorders characterized by recurrent attacks of dystonia, chorea, athetosis, or their combination, with large phenotypic...
Paroxysmal dyskinesias (PD) are rare movement disorders characterized by recurrent attacks of dystonia, chorea, athetosis, or their combination, with large phenotypic and genetic heterogeneity. 3-Hydroxy-isobutyryl-CoA hydrolase () deficiency is a neurodegenerative disease characterized in most patients by a continuous decline in psychomotor abilities or a secondary regression triggered by febrile infections and metabolic crises.We describe two PD patients from two pedigrees, both carrying a homozygous c.913A > G, p.Thr305Ala mutation in the gene, associated with an unusual clinical presentation. The first patient presented in the second year of life with right paroxysmal hemidystonia lasting for 30 minutes, without any loss of consciousness and without any triggering factor. The second patient has presented since the age of 3 recurrent exercise-induced PD episodes which have been described as abnormal equinovarus, contractures of the lower limbs, lasting for 1 to 4 hours, associated with choreic movements of the hands. Their neurological examination and metabolic screening were normal, while brain magnetic resonance imaging showed abnormal signal of the pallidi.We suggest that deficiency, through the accumulation of metabolic intermediates of the valine catabolic pathway, leads to a secondary defect in respiratory chain activity and pyruvate dehydrogenase () activity and to a broad phenotypic spectrum ranging from Leigh syndrome to milder phenotypes. The two patients presented herein expand the spectrum of the disease to include unusual paroxysmal phenotypes and deficiency should be considered in the diagnostic strategy of PD to enable adequate preventive treatment.
Topics: Abnormalities, Multiple; Amino Acid Metabolism, Inborn Errors; Chorea; Humans; Neurodegenerative Diseases; Thiolester Hydrolases
PubMed: 33506479
DOI: 10.1055/s-0040-1722678 -
Brain and Nerve = Shinkei Kenkyu No... May 2023Abnormal involuntary movement (AIM) are usually classified into hypokinesia and hyperkinesia group. Hyperkinesia-AIM includes myoclonus, chorea, ballism, dystonia,...
Abnormal involuntary movement (AIM) are usually classified into hypokinesia and hyperkinesia group. Hyperkinesia-AIM includes myoclonus, chorea, ballism, dystonia, athetosis, and more. Of these, dystonia, myoclonus, and chorea are frequent movement disorders. From a neurophysiological point of view, the mechanism of motor control by the basal ganglia is thought to consist of three pathways: hyperdirect, direct, and indirect. Hyperkinetic-AIMs are likely caused by the dysfunction of any of these three pathways, leading to malfunction in either presurround inhibition, initiation of motor performance, or postsurround inhibition. These dysfunctions are assumed to stem from regions, such as the cerebral cortex, white matter, basal ganglia, brainstem, and cerebellum. Drug therapies that consider the pathogenesis mechanism are desirable. Here, we presented an overview of treatment methods for hyperkinetic-AIMs.
Topics: Humans; Chorea; Myoclonus; Dystonia; Hyperkinesis; Movement Disorders; Dyskinesias
PubMed: 37194528
DOI: 10.11477/mf.1416202375 -
Journal of Neuroengineering and... Mar 2020In this systematic review we investigate which instrumented measurements are available to assess motor impairments, related activity limitations and participation...
BACKGROUND
In this systematic review we investigate which instrumented measurements are available to assess motor impairments, related activity limitations and participation restrictions in children and young adults with dyskinetic cerebral palsy. We aim to classify these instrumented measurements using the categories of the international classification of functioning, disability and health for children and youth (ICF-CY) and provide an overview of the outcome parameters.
METHODS
A systematic literature search was performed in November 2019. We electronically searched Pubmed, Embase and Scopus databases. Search blocks included (a) cerebral palsy, (b) athetosis, dystonia and/or dyskinesia, (c) age 2-24 years and (d) instrumented measurements (using keywords such as biomechanics, sensors, smartphone, and robot).
RESULTS
Our search yielded 4537 articles. After inspection of titles and abstracts, a full text of 245 of those articles were included and assessed for further eligibility. A total of 49 articles met our inclusion criteria. A broad spectrum of instruments and technologies are used to assess motor function in dyskinetic cerebral palsy, with the majority using 3D motion capture and surface electromyography. Only for a small number of instruments methodological quality was assessed, with only one study showing an adequate assessment of test-retest reliability. The majority of studies was at ICF-CY function and structure level and assessed control of voluntary movement (29 of 49) mainly in the upper extremity, followed by assessment of involuntary movements (15 of 49), muscle tone/motor reflex (6 of 49), gait pattern (5 of 49) and muscle power (2 of 49). At ICF-CY level of activities and participation hand and arm use (9 of 49), fine hand use (5 of 49), lifting and carrying objects (3 of 49), maintaining a body position (2 of 49), walking (1 of 49) and moving around using equipment (1 of 49) was assessed. Only a few methods are potentially suitable outside the clinical environment (e.g. inertial sensors, accelerometers).
CONCLUSION
Although the current review shows the potential of several instrumented methods to be used as objective outcome measures in dyskinetic cerebral palsy, their methodological quality is still unknown. Future development should focus on evaluating clinimetrics, including validating against clinical meaningfulness. New technological developments should aim for measurements that can be applied outside the laboratory.
Topics: Adolescent; Cerebral Palsy; Child; Disability Evaluation; Disabled Persons; Humans; Motor Disorders; Young Adult
PubMed: 32138731
DOI: 10.1186/s12984-020-00658-6 -
Frontiers in Veterinary Science 2015Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements,... (Review)
Review
Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements, and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis, and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e., dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans and summarizes similar hereditary movement disorders reported in domestic animals.
PubMed: 26664992
DOI: 10.3389/fvets.2015.00065 -
A Proposed Diagnostic Algorithm for Inborn Errors of Metabolism Presenting With Movements Disorders.Frontiers in Neurology 2020Inherited metabolic diseases or inborn errors of metabolism frequently manifest with both hyperkinetic (dystonia, chorea, myoclonus, ataxia, tremor, etc.) and... (Review)
Review
Inherited metabolic diseases or inborn errors of metabolism frequently manifest with both hyperkinetic (dystonia, chorea, myoclonus, ataxia, tremor, etc.) and hypokinetic (rigid-akinetic syndrome) movement disorders. The diagnosis of these diseases is in many cases difficult, because the same movement disorder can be caused by several diseases. Through a literature review, two hundred and thirty one inborn errors of metabolism presenting with movement disorders have been identified. Fifty-one percent of these diseases exhibits two or more movement disorders, of which ataxia and dystonia are the most frequent. Taking into account the wide range of these disorders, a methodical evaluation system needs to be stablished. This work proposes a six-step diagnostic algorithm for the identification of inborn errors of metabolism presenting with movement disorders comprising red flags, characterization of the movement disorders phenotype (type of movement disorder, age and nature of onset, distribution and temporal pattern) and other neurological and non-neurological signs, minimal biochemical investigation to diagnose treatable diseases, radiological patterns, genetic testing and ultimately, symptomatic, and disease-specific treatment. As a strong action, it is emphasized not to miss any treatable inborn error of metabolism through the algorithm.
PubMed: 33281718
DOI: 10.3389/fneur.2020.582160 -
Journal of Child Neurology May 2022Subacute sclerosing panencephalitis is a progressive devastating condition due to persistence of mutant measles virus, affecting children and adolescents, characterised...
Subacute sclerosing panencephalitis is a progressive devastating condition due to persistence of mutant measles virus, affecting children and adolescents, characterised by myoclonus, seizures, and neuropsychiatric issues. Movement disorders apart from myoclonus are reportedly uncommon. We aimed to describe frequency and proportion of movement disorders among children with subacute sclerosing panencephalitis, hypothesizing that these occur more frequently than previously reported. In this cross-sectional study, we enrolled children with subacute sclerosing panencephalitis between 1 month and 18 years of age who fulfilled the diagnosis of subacute sclerosing panencephalitis as per modified Dyken criteria, and examined them for movement disorders. We also assessed their clinical profile and disease severity via Jabbour staging and modified Rankin Scale score. We compared demographic, clinical, and laboratory features of children with and without movement disorders. We enrolled 50 children (36 males; 72%) (age range 1.5-14 years). Of these, 28 (56%) had movement disorders. Among movement disorders, the most frequent was myoclonus (92%), followed by ataxia (9; 18%), chorea-athetosis (7; 14%), dystonia (6; 12%), tremor (4; 8%), repetitive behavior (4; 8%), and parkinsonism (3; 6%). Movement disorders were the presenting feature of subacute sclerosing panencephalitis among 7 children. There were no significant differences in clinical or laboratory features among children with and without movement disorders. Movement disorders were frequent in subacute sclerosing panencephalitis. Hyperkinetic disorders were dominant. Dystonia and chorea-athetosis occurred more commonly among nonmyoclonus movement disorders. Movement disorders may manifest even in earlier stages of subacute sclerosing panencephalitis and may be the heralding feature. Recognition of these features is important to plan management and reduce morbidity.
Topics: Adolescent; Athetosis; Child; Child, Preschool; Chorea; Cross-Sectional Studies; Dystonia; Electroencephalography; Humans; Infant; Male; Movement Disorders; Myoclonus; Subacute Sclerosing Panencephalitis
PubMed: 35262436
DOI: 10.1177/08830738221085158 -
PM & R : the Journal of Injury,... Mar 2022Balance impairment is a common feature in people with cerebral palsy (CP), affecting the performance of daily-life and physical activities.
BACKGROUND
Balance impairment is a common feature in people with cerebral palsy (CP), affecting the performance of daily-life and physical activities.
OBJECTIVES
To (1) explore the absolute and relative intrasession reliability of two balance tests to assess dynamic and static balance in ambulant para-athletes with CP; (2) explore the relationships between the two balance tests to determine potential application in sport classification; (3) assess the differences between CP profiles (ie, spastic diplegia, athetosis/ataxia, and spastic hemiplegia) in comparison to those with a minimum impairment; and (4) compare the outcomes of the static and dynamic balance of ambulant para-athletes with CP regarding controls.
METHODS
A group of 129 male well-trained para-footballers with CP, classified as Level I according to the Gross Motor Function Classification System, participated in the present study. Static balance was assessed using the One-Leg Stance test, performed bilaterally on a force platform, and the dynamic balance was assessed in two conditions of the Tandem Walk test (TW): walking heel-toe contact over a 5 -m straight line and performing 10 steps.
RESULTS
Moderate-to-excellent intrasession reliability (intraclass correlation coefficient = 0.60-0.98) was obtained for all the measurements and groups. However, only small to moderate correlations were found between the dynamic and the static measurements of balance for the CP group when performing the One-Leg Stance test with the unimpaired or dominant leg (0.23 < r < 0.30; P < .01). The TW performed over 10 steps revealed more sensitivity to discriminate between CP profiles. Those para-athletes with ataxia/athetosis performed worse in all the tests whereas all CP profiles performed worse than the control group (P < .01).
CONCLUSIONS
Balance performance and postural control are constrained to a higher extent in those with impaired voluntary control due to ataxia or with involuntary contractions of the muscles due to athetosis.
Topics: Cerebral Palsy; Exercise; Hemiplegia; Humans; Male; Para-Athletes; Postural Balance; Reproducibility of Results
PubMed: 33599066
DOI: 10.1002/pmrj.12579 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Jun 2021To summarize the genotype and phenotype of epilepsy in patients with interferon regulatory factor 2 binding protein-like (IRF2BPL) gene variants. Data of 6 epilepsy...
To summarize the genotype and phenotype of epilepsy in patients with interferon regulatory factor 2 binding protein-like (IRF2BPL) gene variants. Data of 6 epilepsy patients with IRF2BPL gene variants seen from May 2017 to September 2020 in the Department of Pediatrics of Peking University First Hospital were retrospectively collected. The clinical characteristics and genetic test results were analyzed. A total of 6 patients with IRF2BPL gene variants (1 boy and 5 girls) were identified. The age of seizure onset was from 3.5 to 7.0 months. Epileptic spasms were observed in 6 patients, tonic seizures and tonic-spasms were observed in 1 patient and focal seizure was observed in 1 patient. All 6 patients presented with developmental delay, 5 patients presented with hypotonia, and 2 patients presented with dysphagia. Microcephaly,nystagmus,chorea and athetosis were observed in 1 patient. The electroencephalography (EEG) showed slow background activity in 2 patients. Hypsarrhythmia was observed in all 6 patients. Focal epileptic discharges were observed in 2 patients. Epileptic spasms were monitored in all 6 patients. Focal seizure and tonic-spasm were monitored in 2 patients respectively. The brain magnetic resonance imaging (MRI) showed cerebral atrophy and dysplasia of the corpus callosum in 1 patient, delayed myelination in 2 patients and normal in 3 patients. Two patients had missense variants c.1280C>T/p.L474F and c.1420C>T/p.S427L, 3 patients had frameshift variants c.232delG/p.V78Sfs*73, c.244del/p.A82Pfs*70 and c.283-308del/p.Ala95Thrfs*29, 1 patient had non-frameshift deletion variant c.1453-c.1455delTTC/p.F485del, and all of the 6 cases had de novo variants. All patients were diagnosed with infantile spasms. The last follow-up age ranged from 1 year to 3.8 years. Four patients achieved seizure-free and 2 patients still had frequent seizures after the treatment with antiepileptic drugs (adrenocorticotropic hormone, topiramate, and vigabatrin). IRF2BPL gene variants are mainly de novo. The age of seizure onset is mainly in infancy, and epilepsy and developmental delay are the main clinical manifestations. Infantile spasm is the main phenotype, some patients have hypotonia and dysphagia. Cerebral atrophy can be observed in a few patients.
Topics: Carrier Proteins; Child; Electroencephalography; Epilepsy; Female; Humans; Infant; Male; Nuclear Proteins; Retrospective Studies; Seizures; Spasms, Infantile
PubMed: 34102826
DOI: 10.3760/cma.j.cn112140-20201219-01114