To investigate the potential value of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) on a 3 Tesla MRI system to visualize the spinal cord in SMA patients and to investigate motor connectivity in vivo in patients with SMA.
ID
Source
Brief title
Condition
- Neurological disorders congenital
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters will be both qualitative in terms of anatomy based on
the anatomical MR images, and quantitative in terms of diffusion parameters
including the fractional anisotropy, mean diffusivity, axial diffusivity and
radial diffusivity. Structural changes will be regarded in relation to clinical
characteristics (e.g. duration of illness, disease progression), genetic
factors and clinical scores.
Secondary outcome
N/A.
Background summary
Spinal muscular atrophy (SMA) is a disorder characterized clinically by axial
and proximal muscle weakness and pathologically by degeneration of α-motor
neurons, and is caused by the homozygous deletion of the survival motor neuron
(SMN) 1 gene. It is the most common genetic cause of infant mortality and
causes significant disability and morbidity in survivors. The highly homologous
SMN2 gene produces low amounts of functional SMN mRNA in patients with SMA,
resulting in varying levels of SMN protein deficiency. SMN is important for RNA
splicing and axonal transport, but the mechanisms that cause SMA are largely
unknown. Recent findings in SMA animal models suggest that SMN deficiency
causes abnormal connectivity of α-motor neurons with muscle at the
neuromuscular junction (NMJ) and with sensory afferents in the spinal cord.
Reduced connectivity of motor neurons may therefore be an important cause for
muscle weakness in SMA. We have recently found that dysfunction of the
neuromuscular junction is common in patients with SMA, which suggests that
reduced pre- and postsynaptic connectivity of motor neurons is indeed an
important characteristic of SMA. Robust biomarkers for SMA severity and disease
progression are needed because the relatively slow rate of progression has
complicated the selection of clinical outcome measures for clinical trials. We
hypothesise that reduced connectivity can be visualised in the spinal cord by
using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). DTI
could be helpful as a biomarker to evaluate efficacy of experimental treatment
strategies. We believe that the results of this study may help to gain more
insight in both pathogenic mechanisms and the applicability of DTI as a
biomarker for disease severity in SMA patients.
Study objective
To investigate the potential value of magnetic resonance imaging (MRI) and
diffusion tensor imaging (DTI) on a 3 Tesla MRI system to visualize the spinal
cord in SMA patients and to investigate motor connectivity in vivo in patients
with SMA.
Study design
Observational cross-sectional pilot study (time frame: 12 months)
Study burden and risks
Participants will undergo a clinical assessment and MRI at the University
Medical Center (UMC) Utrecht. There are no known risks associated with MRI,
besides temporary dizziness and claustrophobia. No contrast is needed. There
are no direct benefits for the individual participant. We expect that the
information acquired by this research project will provide new insights in the
pathogenesis of SMA.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Age 12 years or older
- Capable of thoroughly understanding the study information given
- Given written informed consent;Additional inclusion criteria for SMA patients:
- A diagnosis of SMA type 2 or 3, diagnosed on clinical grounds and confirmed by homozygous deletion of the SMN1 gene;;Additional inclusion criteria for healthy volunteers:
- Controls are healthy and do not have any history of SMA or other neuropathy related diseases;
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Tracheostomy, tracheostomal ventilation of any type, (non)-invasive ventilation
- Presence of pronounced swallowing disorders or orthopnoea (which make it dangerous to lie supine in the MRI scanner)
- Forced Vital Capacity >15% postural change between sitting and supine or symptoms of nocturnal hypoventilation (recurrent morning headaches, nightsweats, orthopneu).
- Contra-indications for MRI (e.g. a pacemaker, claustrophobia, pregnancy)
- Previous trauma or surgery of the (cervical) spine
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL52615.041.15 |