OVERVIEW
Multifocal motor neuropathy (MMN), also known as multifocal demyelinating motor neuropathy, is a chronic multifocal mononeuropathy with predominantly motor nerve involvement and a rare demyelinating peripheral neuropathy. Its clinical manifestations are progressive asymmetric limb weakness with predominantly distal involvement. The electrophysiologic feature is the presence of persistent multifocal conduction blocks on the motor nerves.
Etiology
Little is known about the etiology of this disease. It is currently hypothesized that it may be related to Campylobacter jejuni infection, and it is possible that the lipopolysaccharide component (LPS) of Campylobacter jejuni has a role in inducing the production of anti-ganglioside antibodies. There is at least two lines of evidence suggesting an autoimmune association with the development of this disease, namely, elevated serum anti-ganglioside GM1 antibodies in some patients and the fact that a significant proportion of patients are effective on treatment with immunosuppressive drugs (intravenous immunoglobulin and cyclophosphamide).
Symptoms.
The disease is prevalent in 20 to 80 years old, most common in men, the main manifestation is progressive asymmetric limb weakness, mainly distal involvement, there may be very mild sensory impairment, often accompanied by myasthenia gravis, myasthenia gravis and myasthenia gravis are not parallel to each other, limb motor dysfunction is the prominent manifestation, upper and lower extremities can be involved, upper extremities are heavier than the lower extremities, distal is heavier than proximal. A few patients may have transient shoulder pain and mild sensory abnormalities, but there is no definite and constant sensory impairment.
Examination
1. Laboratory tests
Serum phosphokinase is mildly or moderately elevated, and cerebrospinal fluid is positive for high titer anti-GM1 antibody.
2. Peripheral nerve biopsy
It is an important laboratory test for differential diagnosis of peripheral neuropathy.
3. Neuromuscular electrophysiologic examination
The characteristic changes are persistent, multifocal and partial motor conduction block. The latter refers to the reduction of the amplitude and area of the compound muscle action potential produced by stimulating the motor nerves at two points selected from the proximal and distal ends of the limb, and the decrease is mostly greater than 20%, and sometimes it can be as high as 70% or more, and is not accompanied by an abnormal transient dispersed phase. Conduction block may occur in multiple peripheral nerves or in different segments of the same nerve, and is easily detected in the ulnar, median, and radial nerves.
Diagnosis
1. Core criteria (both need to be met)
(1) Slowly progressive or step-like progression of limited asymmetric limb weakness, i.e., at least two or more motor innervations are involved and symptoms persist for more than 6 months; only probable MMN is diagnosed if symptoms and signs are seen in only one innervated area;
(2) No objective sensory deficits, except for minor vibratory sensory abnormalities visible in the lower extremities.
Clinical support criteria: (1) Mainly involving the upper limbs; (2) Weakness or disappearance of tendon reflexes; (3) Cranial nerves are not involved; (4) Painful spasms and fasciculations can be seen in the involved limbs; (5) Immunosuppressive drugs have an ameliorating effect on dysfunction and muscle strength;
Exclusion criteria: ① upper motor neuron signs; ② clear bulbar involvement; ③ severe sensory deficits; ④ diffuse symmetric weakness in the first few weeks.
2. Electrophysiologic criteria
Confirmed motor conduction block:
(1) ≥50% reduction in the negative peak area of the compound muscle action potential (CMAP) proximal compared to distal, regardless of the length of the nerve (median, ulnar, and peroneal) segments. When stimulating the distal portion of segments with motor conduction block, the CMAP negative peak amplitude must be >20% of the low limit of normal and >1 mV, and the CMAP negative peak time frame must increase ≤30% proximal compared to distal.
(2) Probable motor conduction block: ≥30% decrease in CMAP negative peak area when the CMAP negative peak time limit proximal to the distal increases by ≤30% across a long segment (e.g., wrist to elbow or elbow to axilla) of the upper extremity; or ≥50% decrease in CMAP negative peak area when the CMAP negative peak time limit proximal to the distal increases by >30% across a long segment (e.g., wrist to elbow or elbow to axilla) of the upper extremity.
(3) Normal sensory conduction examination of upper extremity ganglia with conduction block.
Differential Diagnosis
It should be differentiated from diseases such as chronic Guillain-Barré syndrome (CIDP) and amyotrophic lateral sclerosis (ALS or SMA).
Treatment
The disease is a treatable condition. High-dose cyclophosphamide shock therapy, followed by maintenance doses orally, results in improvement of clinical symptoms and a significant decrease in serum GM1 antibody titers in most patients. High-dose immunoglobulin therapy for MMN is also effective.
Prognosis
The prognosis of the disease is relatively favorable. The disease progresses slowly in most patients, and some patients are often unable to take care of themselves in daily life due to muscle weakness. There may be periods of plateau and spontaneous remission of varying duration.