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| Name | Class |
|---|---|
| University Hospital, Toulouse | OTHER |
| Universität Tübingen | OTHER |
| University Hospital Tuebingen | OTHER |
| Sykehuset i Vestfold Hospital Trust |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Children with non-progressive congenital ataxia (NPCA) | Eligible population: male and female children, aged 5 to 8 years at time of clinical examination, with a confirmed diagnosis of non-progressive congenital ataxia (NPCA)/Ataxic cerebral palsy, according to SCPE criteria. Participants are recruited from eight European countries (France, Belgium, Denmark, Germany, Greece, Norway and Sweden) through university and regional hospitals, outpatient neurology/rehabilitation clinics and CP registries. Standardized data collection will include comprehensive clinical evaluation, brain MRI (review of images from neonatal or post neonatal periods), genetic analyses, assessment of children's quality of life and parental psychological health. Genetics: Genomic and transcriptomic analyses Advanced genomic analyses (exome, genome, RNA-seq) performed on existing or newly collected blood samples from children with NPCA/ataxic CP to identify disease-associated variants. This includes re-analysis of existing sequencing data and/or new datasets. |
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| Measure | Description | Time Frame |
|---|---|---|
| Characterization of NPCA/ataxic CP | Characterization of non-progressive congenital ataxia(NPCA)/ataxic cerebral palsy (CP) through integrated analysis of clinical features, brain imaging, and advanced genomic testing | At time of clinical examination, between ages 5 and 8 years, and review of MRI and genetic findings |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical characterisation | 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). | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
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Inclusion Criteria: • male or female children
Exclusion Criteria: Children with all other diagnoses of movement disorders or other CP subtypes
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Children, aged 5 to 8 years at time of data collection, with a confirmed diagnosis of NPCA/ataxic CP (according to SCPE criteria), will be identified through university hospitals, regional hospitals, outpatient neurology / rehabilitation clinics, and CP registries, in eight European participating countries (France, Belgium, Denmark, Germany, Greece, Norway, Hungary and Sweden). Recruitment will take place during routine follow-up or planned clinical visits.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kate Himmelmann, MD PhD | Contact | +46 702225589, +46 722039472 | kate.himmelmann@vgregion.se | |
| Catherine Arnaud | Contact | +33 05 67 77 12 85 | catherine.arnaud@utoulouse.fr |
| Name | Affiliation | Role |
|---|---|---|
| Catherine Arnaud, MD PhD | University Hospital of Toulouse | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| KU Leuven | Leuven | Belgium |
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Supporting information
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| ID | Term |
|---|---|
| C562856 | Cerebral Palsy, Ataxic, Autosomal Recessive |
| D065886 | Neurodevelopmental Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
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| UNKNOWN |
| Aarhus University Hospital | OTHER |
| KU Leuven | OTHER |
| Sahlgrenska University Hospital | OTHER |
| Göteborg University | OTHER |
| IASO Children's Hospital, Maroussi, Athens, Greece | UNKNOWN |
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Whole blood samples (EDTA) and PAXgene blood samples will be retained for genomic and transcriptomic analyses. Samples may be obtained from affected children and, when available, from parents and similarly affected siblings. DNA will be extracted for whole genome sequencing, and RNA for transcriptome analysis.
| Cognition and neuropsychiatric features | 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). | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Speech | Impairment profile: Speech is classified using the Viking Speech Scale (VSS) I-IV where level IV is the least functional level | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Communication | Impairment profile: Communication is classified using the the Communication Function Classification System (CFCS) I-V, where level V is the least functional level | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Gross motor function | Gross motor function is classified with the Gross Motor Function Classification System levels I-V, where level V is the least functional level | At time of examination at 5 to 8 years of age |
| Fine motor function | Fine motor function is classified with the Bimanual Fine Motor Function classification (BFMF) levels I-V, where level V is the least functional level | At time of examination at 5 to 8 years of age |
| Manual ability | Manual ability is classified with the Manual Ability Classification System (MACS) level I-V where level V is the least functional level | At time of examination at 5 to 8 years of age |
| Epilepsy | Epilepsy type is documented Focal/generalized/multiple types | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Epilepsy characteristics | :Frequency of seizures last year Seizure-free/seldom or monthly/weekly or daily/cluster or unclear | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Epilepsy treatment | Antiseizure treatment is documented none/monotherapy/Polytherapy/other treatment (surgery, ketogenic diet, vagal nerve stimulation) | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Onset of epilepsy | Age at onset of epilepsy is documented During first year/second year/third year/fourth year/fifth year or later | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Visual impairment | Vision impairments are documented yes/no If yes: severe: yes/no Severe: <0.1 (Decimal scale) in the better eye after correction | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Hearing impairment | 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 | [Time Frame: At time of clinical assessment, between ages 5 and 8 years] |
| Magnetic Resonance Imaging (MRI) | 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 | through study completion, an average of 1 year |
| Genomic analysis | 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. | through study completion, an average of 1 year |
| Family interactions with healthcare system and care utilization | 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. | through study completion, an average of 1 year |
| Child´s quality of life (proxy-reported) | 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. | through study completion, an average of 1 year |
| Perceived family burden (parent report) | 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. | through study completion, an average of 1 year |
| Parental psychological health (parent report) | Parental psychological health is reported using General Health Questionnaire (GHQ-12) Total score 0-36, higher results indicate that the parents experience psychological distress | through study completion, an average of 1 year |
| Aarhus University Hospital | Aarhus | Denmark |
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| Toulouse University Hospital | Toulouse | France |
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| University Hospital Tübingen | Tübingen | Germany |
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| IASO Children's Hospital | Athens | Greece |
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| Vestfold Hospital Trust | Tønsberg | Norway |
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| Queen Silvia Children's Hospital at Sahlgrenska University Hospital | Gothenburg | 416 50 | Sweden |
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