Spinal Muscular Atrophy
Conditions
Interventions
None listed
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1 a. SMA patients i. Patients with SMA from the treatment naive cohort will be included following the predefined criteria: 1) a diagnosis of SMA type 2 or 3, diagnosed on clinical grounds and confirmed by homozygous deletion of the SMN1 gene; 2) given oral and written informed consent ii. Patients with SMA eligible for therapy will be included following the predefined criteria: 1) a diagnosis of SMA type 1-4, diagnosed on clinical grounds and confirmed by homozygous deletion of the SMN1 gene; 2) given oral and written consent by: - patient and parents or legal guardians when patient is between 12-15 years - parents or legal guardians when patient is under 12 years iii. Aged 6 years and older b. Healthy control subjects without manifest diagnosis of motor neuron disease or myopathy i. given oral and written informed consent 2. Capable of thoroughly understanding the study information given
Exclusion criteria
Exclusion criteria: 1. Tracheostomy, tracheostomal ventilation of any type, (non)-invasive ventilation 2. Any intoxication or medication known to have an association with motor neuron dysfunction, which might confound or obscure the diagnosis of motor neuron disease. 3. Presence of pronounced swallowing disorders or orthopnoea (which make it dangerous to lie supine in the MRI scanner) 4. Contra-indication for 3 Tesla MRI (as established by the radiology department) 5. Pregnancy 6. Forced Vital Capacity >15% postural change between sitting and supine or symptoms of nocturnal hypoventilation (recurrent morning headaches, nightsweats, orthopneu). 7. Presence of non-MRI compatible material in the body 8. Claustrophobia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Muscle fat fraction as quantified with DIXON method (based on a chemical shift method for water-fat separation. 2. Changes in tissue composition of muscle, as quantified with T2 mapping (based on the transverse relaxation time of water in tissue). 3. Tissue architecture visualized using Diffusion Tensor Imaging (DTI), further enabling 3D reconstruction of tissue and quantification of microstructural properties (based on fiber tractography (FT) and fractional anisotropy (FA) together with mean diffusity (MD)). 4. Structures of spinal cord and nerve roots visualized with MR images and DTI for qualitative and quantitative assessment. | — |
Secondary
| Measure | Time frame |
|---|---|
| The structural and functional changes will be regarded in relation to genotype (= SMN2 copynumber, a disease modifier) and clinical parameters. Clinical parameters include: age, gender, age at onset of disease, Forced Vital Capacity, disease severity (as measured by the SMA-FRS questionnaire and clinical scores; MRC and dynamometry score and HFMSE combined with upper limb module) and disease duration. | — |
Countries
Netherlands
Outcome results
None listed