To identify (clinical) features of MMN patients that predict a poor clinical disease course. Moge agressive IVIg regimen can be established is this subgroup to maintain functional status of the patient. To find domains in quality of life in MMN…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Natural history:
Clinical disease course is determined by questionnaires and a neurological
examination taken in 2007 and in the current study. Special (clinical) features
is looked for in patients that have poor prognosis.
Quality of life scores compared to the standardized Dutch scores.
Immunological part:
Anti-GM1 IgM titers and HLA haplotyping in MMN and controles
-FcuR status on (subsets of) leukocytes is compared with controls.
- Bacterial cultures that can express GM1 (like) epitopes is compared with
controls.
Secondary outcome
not applicable
Background summary
Multifocal motor neuropathy (MMN) is probably an immune mediated disease with
progressieve paresis of muscles, mainly the hands and to a lesser extend the
feet and arms. Diagnosis may be elusive and the origin of the disease is
unknown. It clinically mimics ALS, but it has a better prognosis and is
treatable with immunoglobulins (IVIg) with a good response. Despite
maintainance therapy, slowly progressive paresis is seen on average. However,
progressive paresis can lead to severe disability in an estimated number of
20%. This is probably due to irreversible axonal degeneration. It is not known
what factors/features this subgroup with a poor clinical outcome has.
Debut of onset is 20-70 year which means that it affect people in their
'active' years, in social as well as in working means.
The origen of MMN is not known. However, there are strong arguments that it is
an immune mediated disease. One of these arguments is the presence of anti-GM1
antibodies in around half of the patients. GM1 is a protein that is abundantly
expressed on peripheral nerves. Binding of the antibody to GM1 leads to
complement activation and forming of the membrane attack complex that damages
the nerve and results in local inflammation. The origin of these antibodies in
snot elucidated yet.
Study objective
To identify (clinical) features of MMN patients that predict a poor clinical
disease course. Moge agressive IVIg regimen can be established is this subgroup
to maintain functional status of the patient.
To find domains in quality of life in MMN patients in which MMN patients
perform worse than the 'normal values' of the Dutch population.
To unravel the origin of the anti-GM1IgM. Possibilities are an endogenous
origin (as a result af deficient IgM receptors on (subsets of) leukocyts or a
linkage with HLA-DRB1*15 haplotype). Another possibility is that it is a result
of an exogenous pathogen, that is able to express GM1 (like) epitopes on its
cell surface and by molecular mimicry the antibodies are produced.
Study design
The goals will be:
- a longitudinal observational study. 88 patients seen in 2007 (METC number
05/273) are re-seen and re-scored by questionnaires (ODSS, FSS, SES) and
neurological examination (MRC sum score) as in 2007.
- studying QoL in a cross sectional setting by taking the sf-36 and USER-P
questionnaires of 120 MMN patients and these results are compared with
validated scores of the Dutch population.
- Disease mechanism in a case cohort study in which bacterial cultures
(especially H. Influenzae) is tested for the presence of GM1 epitopes on their
cell surface. expression of the FcuR is tested on leukocytes of MMN patients
and controls.
Blood samples of MMN patients and controls is further tested for antibody level
and HLA haplotyping.
A second venipuncture will performed to test leukocyte subsets (iNKT cells and
plasmablasts, for more detailled information see the added information in the
introduction in the WMO protocol) in MMN patients and controls.
Study burden and risks
The burden consists of a trip to the hospital and back home, taking
questionnaires (that are estimated of low psychological impact) and a clinical
examination that focusses on the strength, sensitivity and reflexes of the
limbs.
A venapuncture can give local transient pain and/or hematoma, a throat swab can
sometimes give an unpleasant feeling that will last only seconds.
For controls, the burden consist of the throat swab and to draw one extra tube
in an already planned venapuncture
The total time in the hospital will be around 1,5 - 2h for the MMN patients.
Cumulative burden is estimated low and the risk is neglegible.
Concerning the second venipuncture the same burdens as described above are
applicable, except that patients do not come to the hospital for the
venipuncture alone, but they will be asked at their regular appointment at the
outpatient clinic. Total extra time cost is estimated 5 minutes.
Van koetsveldstraat 122
Utrecht 3532ET
NL
Van koetsveldstraat 122
Utrecht 3532ET
NL
Listed location countries
Age
Inclusion criteria
Patients are subjects who fullfil the diagnostic consensus criteria for MMN (see protocol, page 40)
Controls are people who visit the neuromuscular outpatient clinic for diseases other than MMN.
All subjects are older than 18 year, are not mentally incapacitated and fully understand the given information for the study
Exclusion criteria
An MMN patient who meets any of the following criteria will be excluded from participation in this study:
- Doubts about the diagnosis MMN
- Relevant concomitant illnesses (i.e. haematological or immunological diseases) that may interfere with any part of the study
A control will be excluded when any of the following criteria is met:
- having MMN as a diagnosis in the history
- under 18 years old.
- not capable of understanding the given information or giving consent.
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 | NL50354.041.14 |