To assess if resting membrane potential or ion channel activity is abnormal in sensory axons of affected nerves in MMN patients.
ID
Source
Brief title
Condition
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Excitability-variables of motor and sensory axons of the median nerve at the
wrist.
Secondary outcome
Not applicable.
Background summary
Multifocal motor neuropathy (MMN) is a peripheral nerve disorder characterized
by focal lesions which affect only the motor fibers within nerves. MMN results
in muscle weakness and atrophy especially of hand muscles. The pathophysiology
in MMN is unclear because biopsies of peripheral nerves are not possible
without causing additional weakness. One of the points that are unclear is why
the lesions in MMN affect motor axons only and leave neighboring sensory axons
in the same nerve apparently unaffected. This project addresses the hypothesis
that sensory axons in MMN lesions are affected but that they can compensate
this because their ion-channel repertoire slightly differs from that in motor
axons. To investigate this, we will investigate motor and sensory axons in
affected hand nerves of 20 MMN patients by means of excitability-testing. This
is an advanced electrophysiological method enabling non-invasive assessment of
different ion-channel types in peripheral axons.
Study objective
To assess if resting membrane potential or ion channel activity is abnormal in
sensory axons of affected nerves in MMN patients.
Study design
We will investigate 20 MMN patients with conduction block in median nerve motor
axons in the forearm. The median nerve was chosen because the sensory nerve
response for excitability testing is robust. Per patient, two
excitability-tests will be performed on the median nerve at the wrist: one for
motor axons and one for sensory axons. In order to avoid treatment effects on
ion channel function, tests will be performed on the day before starting a new
immunoglobulin course. The investigation takes 1 hour and 30 minutes and
consists of the following procedures:
1. Motor nerve conduction study of the median nerve in the forearm in order to
verify the EMG-abnormalities still occur; this entails delivering electrical
stimuli at the wrist and elbow. Sensory conduction of the median nerve of the
third finger to exclude carpal tunnel syndrome; this is important since carpal
tunnel syndrome affects excitability-variables. Duration: 10 minutes.
2. Warming the forearm and hand to 37°C by wrapping them into a plastic blanket
through which water at 37°C flows. Duration: 30 minutes.
3. Excitability-test of median nerve motor axons at the wrist. Duration: 15
minutes.
4. Excitability-test of median nerve sensory axons at the wrist. Duration: 30
minutes.
5. Clinical assessment of the median nerve by (i) MRC grading of the abductor
pollicis brevis muscle, (ii) joint position sense of the distal phalangeal
joint of the middle finger, (iii) 2-point discrimination of the distal phalanx
of the middle finger. Duration: 5 min.
Study burden and risks
Slight physical discomfort due to electrical stimulation and brief local skin
reddening due to skin electrode adhesive gel may occur. There are no known
risks for the study procedure based on the literature and on our experience in
previous excitability and nerve conduction studies. Patients will benefit
indirectly from the study because more will be known about pathogenetic
mechanisms in MMN which, in turn, may lead to development of treatment
strategies aimed at axonal protection.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
1. Diagnosis of MMN according to internationally accepted criteria of the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS criteria).
2. One median nerve (left or right) with any of the follwing abnormalities in the motor nerve conduction studies:
a) conduction block in motor axons in the forearm segment, defined as segmental reduction of compound muscle action potential (CMAP) area of at least 30%;
b) signs of demyelination: conduction velocity decrease up to 38 m/s or less and/or DML 5.3 ms or more and/or increase CMAP duration in the forearm of at least 30%;
c) motor axon loss defined as decreased CMAP amplitude of 3 mV or less;
3. Age range 18-99 years old.
Exclusion criteria
1. Other causes for neuropathy than MMN, including carpal tunnel syndrome (CTS).
2. Use of medication affecting ion-channels in nerves.
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 | NL53422.041.15 |