Paediatric motor phenotypes in early‐onset ataxia, developmental coordination disorder, and central hypotonia

Lawerman, T.F.; Brandsma, R.; Maurits, Natasha M.; Martinez-Manzanera, Octavio; Verschuuren‐Bemelmans, Corien C.; Lunsing, Roelineke J.; Brouwer, O.F.; Kremer, H.P.H.; Sival, Deborah A

doi:10.1111/dmcn.14355

Cited by 13 publications

(26 citation statements)

References 30 publications

(84 reference statements)

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“…In literature, similar pathologic mechanisms have been proposed in children with developmental coordination disorder (DCD) [33e35]. In children with DCD, we have observed similarly increased SARA scores as in present study group [36]. However, although these similarities may suggest a common ground, this remains entirely speculative as the age of our study group was too young for consideration of the DCD diagnosis (i.e.…”

Section: Retrospective Neonatal Parameterssupporting

confidence: 73%

Dyskinesia Impairment Scale scores in Dutch pre-school children after neonatal therapeutic hypothermia

Kuiper

Meiners

Chandler

et al. 2020

European Journal of Paediatric Neurology

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Background: Neonatal therapeutic hypothermia (TH) can ameliorate or prevent the development of dyskinetic cerebral palsy (CP) after hypoxic-ischemic encephalopathy (HIE). The Dyskinesia Impairment Scale (DIS) was recently launched to quantify dyskinetic (dystonic and choreatic) motor features in patients with CP. In TH treated children, who are at risk of developing dyskinetic CP, we aimed to determine DIS-scores at pre-school age. Method: In 21 Dutch pre-school children (3e6 years of age) who had received TH according to the Dutch-Flemish treatment protocol, we determined DIS-scores. We associated DIS-scores with 1. agematched control values (Kuiper et al., 2018) [1], and 2. previously reported DIS-score range in dyskinetic CP (Monbaliu E et al., 2015). Results: The motor phenotype was determined as: normal (n ¼ 18/21), mildly impaired (reduced coordination (n ¼ 2/21)) and abnormal (dyskinetic CP; n ¼ 1/21). In absence of CP (n ¼ 20/21), DIS-scores were lower (more favorable) than in dyskinetic CP, without any overlapping group scores (mean difference: 71 points; p < .05). However, the obtained DIS-scores were still higher than previously reported in healthy age-matched controls (mean difference: 14 points; p < .05). There was an association between DIS-scores and retrospective neonatal MRI (basal ganglia and thalamus injury on diffusion weighted imaging (DWI)) and (a)EEG parameters (p < .05). Conclusion: In the vast majority (95%) of Dutch TH-HIE treated pre-school children, the phenotypic motor outcome was favorable. However, DIS-scores were moderately increased compared with healthy age-matched controls. Future studies may elucidate the significance of moderately increased DIS-scores should to further extent.

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Section: Retrospective Neonatal Parameterssupporting

confidence: 73%

Dyskinesia Impairment Scale scores in Dutch pre-school children after neonatal therapeutic hypothermia

Kuiper

Meiners

Chandler

et al. 2020

European Journal of Paediatric Neurology

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“…In accordance with previously described methodology [1], we included videotaped SARA (scale for assessment and rating of ataxia [11]) or ICARS (international cooperative ataxia rating scale [12]) performances, that had been video-taped at the outpatient clinic for patient surveillance reasons. Both scales have been shown to capture paediatric ataxic movement disorder features in a similarly reliable way [13,14].…”

Section: Phenotypic Assessmentmentioning

confidence: 99%

“…The diagnosis "early onset ataxia" refers to a group of rare, genetically inheritable diseases with an estimated prevalence of 14.6 per 100,000 individuals, initiated before the 25th year of life. These "ataxic syndromes" involve a heterogeneous group of underlying disorders that may Diagnostics 2020, 10, 997 2 of 17 phenotypically involve: (a) pure ataxic features; (b) predominant ataxic features in combination with other comorbid movement disorder features; (c) mild ataxic features in combination with other primary movement disorder features; (d) hardly discernible, disputable or even absent ataxic features, but with an underlying diagnosis that is phenotypically described as ataxic in the Online Mendelian Inheritance in Man (OMIM) database [1]. Depending on the age of the patient at disease presentation, patients are categorized as 'early onset ataxia' (EOA, i.e., initiation before 25 years of age) or degenerative 'adult onset ataxia' (AOA, i.e., initiation after 25 years of age) [2].…”

Section: Introductionmentioning

confidence: 99%

Early Onset Ataxia with Comorbid Dystonia: Clinical, Anatomical and Biological Pathway Analysis Expose Shared Pathophysiology

et al. 2020

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In degenerative adult onset ataxia (AOA), dystonic comorbidity is attributed to one disease continuum. However, in early adult onset ataxia (EOA), the prevalence and pathogenesis of dystonic comorbidity (EOAD+), are still unclear. In 80 EOA-patients, we determined the EOAD+-prevalence in association with MRI-abnormalities. Subsequently, we explored underlying biological pathways by genetic network and functional enrichment analysis. We checked pathway-outcomes in specific EOAD+-genotypes by comparing results with non-specifically (in-silico-determined) shared genes in up-to-date EOA, AOA and dystonia gene panels (that could concurrently cause ataxia and dystonia). In the majority (65%) of EOA-patients, mild EOAD+-features concurred with extra-cerebellar MRI abnormalities (at pons and/or basal-ganglia and/or thalamus (p = 0.001)). Genetic network and functional enrichment analysis in EOAD+-genotypes indicated an association with organelle- and cellular-component organization (important for energy production and signal transduction). In non-specifically, in-silico-determined shared EOA, AOA and dystonia genes, pathways were enriched for Krebs-cycle and fatty acid/lipid-metabolic processes. In frequently occurring EOAD+-phenotypes, clinical, anatomical and biological pathway analyses reveal shared pathophysiology between ataxia and dystonia, associated with cellular energy metabolism and network signal transduction. Insight in the underlying pathophysiology of heterogeneous EOAD+-phenotype-genotype relationships supports the rationale for testing with complete, up-to-date movement disorder gene lists, instead of single EOA gene-panels.

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“…For example, ataxia‐telangiectasia, spinocerebellar ataxia (SCA), and Joubert syndrome can mimic ataxic CP in early life. Developmental impairment of motor coordination as seen in developmental coordination disorder (DCD) is much more prevalent than these conditions, and in many children one cannot distinguish between motor phenotypes of DCD and degenerative ataxias, not to mention ataxic CP. Admittedly, assessing motor disorders in developing children is challenging, and one cannot rely on widely shared experience as in spastic and dyskinetic CP.…”

mentioning

confidence: 99%

How useful is the diagnosis of ataxic cerebral palsy?

Dan¹

2020

Develop Med Child Neuro

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EDITORIALHow useful is the diagnosis of ataxic cerebral palsy?Cerebral palsy (CP) involves a wide range of clinical presentations. Therefore, it is useful to categorize individuals into groups for clinical, research, and service provision purposes. Cerebellar diplegia or congenital cerebellar ataxia was first described in 1903 by Frederick Batten, who differentiated it from hereditary cerebellar ataxia, 1 but the term 'ataxic CP' is currently used in various ways. According to the Surveillance of Cerebral Palsy in Europe, individuals with ataxic CP show generalized hypotonia with loss of orderly muscle coordination so that movements are performed with 'abnormal' force, rhythm, and accuracy. 2 Other schemes do not require the presence of hypotonia. 3 Experience (and perhaps my own clinical practice bias) suggests that poor balance and intention tremor are typical, gross motor function is generally less impaired than in other types of bilateral CP, individuals are less likely to develop contractures, and intellectual disability and speech impairment are quite common. However, there is a lack of description of motor and non-motor features in the literature, making the diagnosis problematic. Indeed, early-onset ataxia can signal a host of genetic disorders that are often progressive (thus not CP) with poor outcomes. For example, ataxia-telangiectasia, spinocerebellar ataxia (SCA), and Joubert syndrome can mimic ataxic CP in early life. Developmental impairment of motor coordination as seen in developmental coordination disorder (DCD) is much more prevalent than these conditions, and in many children one cannot distinguish between motor phenotypes of DCD and degenerative ataxias, 4 not to mention ataxic CP. Admittedly, assessing motor disorders in developing children is challenging, and one cannot rely on widely shared experience as in spastic and dyskinetic CP.Ataxic CP is the least common CP type, accounting for less than 1 in 10 individuals with CP. Moreover, a higher proportion of children see their diagnosis reassigned to non-CP conditions by age 5 years, indicating incorrect initial diagnosis. 3 Thus, more consequentially than in other presentations, it must be stressed that the diagnosis of CP, even when accurate, is essentially descriptive, calling for a comprehensive aetiological work-up.A genetic origin does not rule out the diagnosis, and it carries counselling implications. 5 Further complexity arises as some responsible genes are better known to cause non-

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Paediatric motor phenotypes in early‐onset ataxia, developmental coordination disorder, and central hypotonia

Cited by 13 publications

References 30 publications

Dyskinesia Impairment Scale scores in Dutch pre-school children after neonatal therapeutic hypothermia

Dyskinesia Impairment Scale scores in Dutch pre-school children after neonatal therapeutic hypothermia

Early Onset Ataxia with Comorbid Dystonia: Clinical, Anatomical and Biological Pathway Analysis Expose Shared Pathophysiology

How useful is the diagnosis of ataxic cerebral palsy?

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