Ataxic Cerebral Palsy, Non-progressive Congenital Ataxia
Conditions
Keywords
Non-progressive Congenital Ataxia, Ataxic Cerebral Palsy, Genetic etiology, Neuroimaging, Neurodevelopmental disorders, Quality of Life
Brief summary
This multinational European observational clinical study focuses on non-progressive congenital ataxia (NPCA), a very rare early-onset neurological condition also within the cerebral palsy (CP) concept as ataxic CP. The study aims to improve the diagnosis and care of affected children through a comprehensive approach that integrates detailed clinical assessments, brain imaging analyses, and advanced genetic testing. By identifying developmental trajectories, specific impairment profiles, brain MRI patterns, and genetic variants, the researchers aim to elucidate underlying mechanisms, origins and clinical heterogeneity of NPCA. The study also assesses the broader impact of the condition on the quality of life of affected children and the associated burden on their families. Preliminary data found a high prevalence of cognitive and neuropsychiatric impairments, and a frequent lack of identifiable brain lesions on MRI, raising the hypothesis of a strong genetic contribution.
Detailed description
Non-progressive congenital ataxia (NPCA), also known as ataxic cerebral palsy (CP), is a very rare (0.8 p 10.000 livebirths) early-onset motor disorder characterized by disordered muscular coordination, affecting the force, rhythm, and accuracy of movements. The ARTEMIS clinical study is a European multinational, multicentre, observational study, designed to study the natural history of NPCA, and investigate the clinical, neuroimaging, and genetic characteristics of NPCA. Its collects comprehensive data from children aged 5 to 8 years with a confirmed diagnosis according to the Surveillance of Cerebral Palsy in Europe (SCPE) definition from neonatal period (retrospective data collection) to time of assessment (5 to 8 years of age). The study involves reference centres across France, Belgium, Denmark, Germany, Greece, Norway, Hungary, and Sweden. The study aims to comprehensively characterize NPCA by assessing clinical impairments, developmental trajectories, brain MRI findings, and genetic data, while also evaluating children's quality of life, parental burden, and healthcare pathways.
Interventions
None listed
Sponsors
Vastra Gotaland Region
University Hospital, Toulouse
Universität Tübingen
University Hospital Tuebingen
Sykehuset i Vestfold Hospital Trust
Aarhus University Hospital
KU Leuven
Sahlgrenska University Hospital
Göteborg University
IASO Children's Hospital, Maroussi, Athens, Greece
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
5 Years to 8 Years
Healthy volunteers
No
Inclusion criteria
• male or female children * confirmed diagnosis of NPCA/Ataxic CP (SCPE definition) * aged ≥ 5 years and ≤ 8 years at time of data collection * written informed consent of at least one parent or legal representative in accordance to country regulations, and verbal assent of the child when possible
Exclusion criteria
Children with all other diagnoses of movement disorders or other CP subtypes \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of NPCA/ataxic CP | At time of clinical examination, between ages 5 and 8 years, and review of MRI and genetic findings | Characterization of non-progressive congenital ataxia(NPCA)/ataxic cerebral palsy (CP) through integrated analysis of clinical features, brain imaging, and advanced genomic testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Speech | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Impairment profile: Speech is classified using the Viking Speech Scale (VSS) I-IV where level IV is the least functional level |
| Communication | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Impairment profile: Communication is classified using the the Communication Function Classification System (CFCS) I-V, where level V is the least functional level |
| Gross motor function | At time of examination at 5 to 8 years of age | Gross motor function is classified with the Gross Motor Function Classification System levels I-V, where level V is the least functional level |
| Fine motor function | At time of examination at 5 to 8 years of age | Fine motor function is classified with the Bimanual Fine Motor Function classification (BFMF) levels I-V, where level V is the least functional level |
| Manual ability | At time of examination at 5 to 8 years of age | Manual ability is classified with the Manual Ability Classification System (MACS) level I-V where level V is the least functional level |
| Epilepsy | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Epilepsy type is documented Focal/generalized/multiple types |
| Epilepsy characteristics | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | :Frequency of seizures last year Seizure-free/seldom or monthly/weekly or daily/cluster or unclear |
| Epilepsy treatment | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Antiseizure treatment is documented none/monotherapy/Polytherapy/other treatment (surgery, ketogenic diet, vagal nerve stimulation) |
| Onset of epilepsy | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Age at onset of epilepsy is documented During first year/second year/third year/fourth year/fifth year or later |
| Visual impairment | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Vision impairments are documented yes/no If yes: severe: yes/no Severe: \<0.1 (Decimal scale) in the better eye after correction |
| Hearing impairment | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Hearing impairments are documented yes/no If yes: severe yes/no Severe Hearing loss greater than 70 decibel (dB) before correction in the better ear |
| Clinical characterisation | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Characterisation of ataxic features using the Scale for the Assessment and Rating of Ataxia (SARA) score Clinical assessment of ataxic and other motor features includes muscle tone, tremor, balance, spasticity, and dystonia. Evaluation with the (SARA), a validated tool with scores from 0 (no ataxia) to 40 (most severe). |
| Magnetic Resonance Imaging (MRI) | through study completion, an average of 1 year | MRI analysis: neuroimaging classification and cerebral/cerebellar volumetry Systematic review of previously acquired (neonatal and/or postneonatal periods) brain MRIs. In the subgroup of children with normal images (group E of the Neonatal Neuroimaging Classification System and Magnetic Resonance Imaging Classification System), in addition cerebellar and cerebral volumetry compared to age- and sex-matched controls to identify structural correlates |
| Genomic analysis | through study completion, an average of 1 year | Identification of disease-associated variants Analysis of existing or newly generated exome/genome sequencing data to identify single nucleotide variants, small insertions/deletions, structural variants, and repeat expansions. |
| Family interactions with healthcare system and care utilization | through study completion, an average of 1 year | Parent questionnaire assessing the child's healthcare journey, including age at first specialist visit, therapies received, multidisciplinary evaluations, access to aids/support, social services, and disability-related resources. |
| Child´s quality of life (proxy-reported) | through study completion, an average of 1 year | Child's quality of life (proxy-reported) using KIDSCREEN-27 Assessment of child's quality of life using the KIDSCREEN-27 questionnaire completed by parents. Includes five domains: physical well-being, psychological well-being, autonomy and parent relations, social support and peers, and school environment. Higher values indicate better quality of life. Population norm mean 50, sd 10. |
| Perceived family burden (parent report) | through study completion, an average of 1 year | Family impact of Childhood Disability (+4) is used to report perceived burden related to time, stress, work, health, finances, and family relationships, assessing impact of child's disability on family well-being. Scores 10-40, higher scores indicate a higher impact on the family. |
| Cognition and neuropsychiatric features | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] | Composite multidimensional assessment of intelligence or developmental quotient (IQ or DQ), Attention-Deficit/Hyperactivity Disorder (ADHD) and/or Autism Spectrum Disorder (ASD) (according to Diagnostic and Statistical Manual of Mental Disorder V criteria). |
| Parental psychological health (parent report) | through study completion, an average of 1 year | Parental psychological health is reported using General Health Questionnaire (GHQ-12) Total score 0-36, higher results indicate that the parents experience psychological distress |
Countries
Belgium, Denmark, France, Germany, Greece, Norway, Sweden
Contacts
CONTACTKate Himmelmann, MD PhD
CONTACTCatherine Arnaud
STUDY_DIRECTORCatherine Arnaud, MD PhD
University Hospital of Toulouse
Outcome results
None listed