To obtain robust evidence for activity-dependent CB and depolarizing CB in CIDP or MMN. This may reveal specific mechanisms of axon loss and provide a rationale for additional treatment aimed at prevention of irreversible axon loss.
Source
Brief title
Condition
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
-indications of or evidence for activity-dependent conduction block
-indications of or evidence for depolarizing conduction block
Secondary outcome
-
Background summary
Chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor
neuropathy (MMN) are immune-mediated nerve disorders characterized by
demyelination. Muscle weakness in both disorders is important and is usually
ascribed to conduction block (CB) of action potentials in severely demyelinated
axons. Our group has shown that axonal degeneration - which also contributes to
weakness- is abundant in MMN ánd the strongest independent determinant of
weakness. We also found a strong correlation of axonal degeneration with CB,
which suggests that clarification of the mechanisms underlying CB may lead to
novel treatment strategies in MMN aimed at prevention of axonal degeneration.
Until now, CB was considered to be caused by a demyelinative disease process.
However, recent studies suggested other mechanisms for weakness than this
static demyelinative CB. First, weakness may increase with sustained
muscle-activity. Prolonged firing yields axonal hyperpolarization due to
increased Na/K-pump activity. This hyperpolarization may cause
activity-dependent CB. Second, weakness in MMN may increase with cold. This
suggests depolarizing CB due to temperature-induced Na/K-pump slowing at sites
where pump-function is already impaired by inflammation. However, the evidence
and importance of these mechanisms are uncertain: few patients were
investigated, nerve conduction studies used to detect CB were methodologically
incorrect, it is unknown whether axonal hyperpolarization also occurs with
natural muscle-activity (e.g., typing), and the impact of activity- and
temperature-induced weakness is unknown.
Study objective
To obtain robust evidence for activity-dependent CB and depolarizing CB in
CIDP or MMN. This may reveal specific mechanisms of axon loss and provide a
rationale for additional treatment aimed at prevention of irreversible axon
loss.
Study design
Cross-sectional and case-control.
Study burden and risks
To our knowledge, participation in this study does not bring along any specific
risks to the subjects. The burden associated with participation is limited. All
subjects will be asked to fill in a questionnaire. Force measurements will be
performed in half of the subjects. Further electrophysiological testing in a
minority of the participants is non-invasive, but some patients may experience
some inconvenience.
The study may result in a rationale for the prevention of irreversible axon
loss which is an important cause for permanent weakness in MMN and CIPD
patients.
NL
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for patients with MMN: 1) weakness and atrophy of the limbs on neurological examination, 2) motor conduction block (CB) on extensive standardized nerve conduction studies according to criteria previously defined by our group.
Inclusion criteria for patients with CIDP: 1) presence of progressive or relapsing motor (muscle weakness) or sensory (numbness, tingling) dysfunction of more than one limb (both proximally and distally), 2) hyporeflexia or areflexia of the limbs, 3) abnormalities on nerve conduction studies indicative of demyelination (conduction block, increased temporal dispersion, absent F-waves or increased F- M latency, or reduction of conduction velocity).
Inclusion criteria for patients with LMND: 1) weakness, atrophy, and fasciculations in the limbs, 2) electrophysiological evidence of lower motor neuron involvement (denervation and/ or reinnervation) on needle EMG examination in clinically affected and nonaffected muscles without evidence of conduction block.
Exclusion criteria
Exclusion criteria for patients with MMN: 1) objective sensory signs on neurological examination, 2) clinical signs of upper motor neuron involvement (pseudobulbar symptoms, clonus of masseter reflex, hyperreflexia hypertonia or extensor plantar responses of the limbs).
Exclusion criteria for patients with CIDP: 1) duration of signs and symptoms shorter than 2 months, 2) elevated (>10/mm3) white cell count of cerebrospinal fluid with elevated protein levels.
Exclusion criteria for patients with LMND: 1) history of diseases that may mimic LMND (acute poliomyelitis, spinal radiculopathy, diabetic amyotrophy, thyrotoxicosis or hyperparathyroidism), 2) clinical signs of upper motor neuron involvement (see above), 3) objective sensory signs on neurological examination.
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 | NL15363.041.06 |