1. Explore the diagnostic value by comparing muscle volume, fatty infiltration and oedema/inflammation using qMRI in MG patients, healthy controls and MG mimics (other neuromuscular diseases and Graves* ophthalmopathy (GO) patients).2. Explore the…
ID
Source
Brief title
Condition
- Ocular neuromuscular disorders
- Muscle disorders
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
(1) QMRI parameters (muscle fat fraction, muscle inflammation, muscle volume)
which are hypothesized to differ between MG patients and the healthy/disease
controls for diagnostic value.
(2) For the second objective comparing recently diagnosed and chronic MG
patients for exploring the pathophysiology
Secondary outcome
(3) For the third objective comparing the qMRI parameters in time in the
recently diagnosed MG group to measures of severity of disease to assess the
predictive value for treatment response.
(4) For the fourth objective comparing qMRI parameters to functional measures
in all groups for exploring the relationship with the symptoms
Background summary
The auto-immune disease myasthenia gravis (MG) affects the neuromuscular
junction (NMJ) and commonly starts with weakness of the extra-ocular muscles
(EOM). In patients with pure EOM symptoms and no acetylcholine receptor (AChR)
antibodies, diagnosis is difficult and time-consuming. This causes significant
burden for patients, delays effective treatment, and possibly increases the
chance of developing generalized MG.
Furthermore, treatment usually consists of immune suppressant medication, of
which corticosteroids are the most commonly prescribed. Unfortunately, long
term steroid use carries a considerable risk of unacceptable side effects.
While immune suppressant treatment leads to a significant improvement in the
majority of patients, 15% show only a moderate improvement or no improvement at
all after treatment with corticosteroids.
In this study, we aim to assess inflammatory and structural changes of EOM with
magnetic resonance imaging (MRI). Our pilot data using quantitative MRI (qMRI)
show structural degenerative changes in the EOM of chronic MG patients, which
has not been described in literature before. We aim to develop a novel
diagnostic paradigm for AChR negative MG and a predictor for treatment efficacy
in all MG patients by systematically comparing qMRI parameters of the EOM in
clearly defined clinical groups of MG patients to healthy and disease controls
(other neuromuscular diseases and Graves* orbitopathy (GO)).
Study objective
1. Explore the diagnostic value by comparing muscle volume, fatty infiltration
and oedema/inflammation using qMRI in MG patients, healthy controls and MG
mimics (other neuromuscular diseases and Graves* ophthalmopathy (GO) patients).
2. Explore the pathophysiology by comparing these qMRI parameters in recently
diagnosed and chronic MG patients
3. Explore whether these qMRI parameters can predict response to treatment by
comparing these qMRI parameters in time to measures of severity of disease.
4. Explore the relationship to the symptoms by comparing these qMRI parameters
to functional measures of each individual extraocular muscle.
Study design
The study is an observational case-control study. All participants will undergo
an MRI scan In addition, functional measures will be obtained to quantify
symptoms, fatigability and function of the extraocular muscles for comparison
to the qMRI parameters. One group with recently diagnosed MG patients will
undergo one follow-up measurement after six months.
Study burden and risks
This study has no invasive procedures. Subjects with contraindications for MRI
will be excluded. There are no known risks known associated with the use of MRI
and the ophthalmologic measures performed. Participants have no personal
benefit from participating in this study. However, the results study may
contribute to the diagnosis and predictability of therapeutic response in all
MG patients.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Age
Inclusion criteria
Recently diagnosed MG patients
- Definitive diagnosis of MG defined as the presence of serum autoantibodies
(anti-acetylcholine receptor [AChR], anti-muscle specific tyrosine kinase
[MuSK])
- Start of symptoms was less than a year ago
- No corticosteroid treatment received in the past year
- No TSH-receptor auto-antibodies, no laboratory signs of thyroid dysfunction
(T4, TSH), Chronic MG patients
- Definitive diagnosis of MG, defined as described above
- Persisting symptoms of diplopia
- Start of symptoms was more than a year ago
- No TSH-receptor auto-antibodies, no laboratory signs of thyroid dysfunction
(T4, TSH), Seronegative MG patients
- Clinical diagnosis of MG with asymmetric, fluctuating and fatigable muscle
weakness and at least one abnormal neurophysiological test, indicative of
neuromuscular dysfunction (repetitive nerve stimulation or single fiber EMG)
- No serum autoantibodies (anti-acetylcholine receptor [AChR], anti-muscle
specific tyrosine kinase [MuSK])
- No TSH-receptor auto-antibodies, no laboratory signs of thyroid dysfunction
(T4, TSH)
Healthy controls
- No symptoms of diplopia
- No ophthalmopathy
- No prior systemic treatment with corticosteroids, Patient controls: Graves*
orbitopathy
- Definitive diagnosis of Graves* orbitopathy, Patient controls: Other
neuromuscular disease
- Definitive diagnosis of a neuromuscular disease other than Myasthenia gravis
Exclusion criteria
- Subjects who are not legally capable
- Subjects under the age of 18
- Contraindications to MRI scanning, including:
o Claustrophobia
o Pregnancy
o Pacemakers and defibrillators
o Nerve stimulators
o Intracranial clips
o Metallic fragments
o Cochlear implants
o Ferromagnetic implants
o Hydrocephalus pump
o Permanent make-up
o Tattoos above the shoulders
o Piercings (unless they can be removed)
o Subjects who cannot keep their head still (eg. Tremor, Parkinson*s disease)
o Severe physical restriction (completely wheelchair dependent)
* In the case of uncertainty about the MRI-contraindications, the MR-safety
commission of the radiology department will decide whether this subject can be
included in the study or not.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL68612.058.18 |
| OMON | NL-OMON23441 |