Overview.
Monoclonal gammopathy combined with peripheral neuropathy is also called paraproteinemic peripheral neuropathy. The presence of excess M protein in the blood is called monoclonal gammopathy, also known as immunoglobulinopathy, paraproteinopathy, or plasma cell disease. The pathological significance of the presence of M proteins in the blood for peripheral nerves lies in the fact that the M proteins contain one or more antibodies against the myelin sheath or axonal membrane, such as anti-MAG, GM1, and GD1 antibodies. Among idiopathic peripheral neuropathies of undetermined cause, 10% are comorbid with monoclonal gammopathy, while monoclonal gammopathy of undetermined significance (MGUS) is comorbid with peripheral neuropathy in 29% to 71%, suggesting that monoclonal gammopathy is associated with peripheral neuropathy.
Etiology.
Monoclonal gammopathies, immunoglobulinopathies, paraproteinemias, and intracellular protein abnormalities, a group of diseases also known as plasmacytosis, are a group of neoplastic or tumor predisposed disorders caused by monoclonal plasma cells derived from immune B-cell lineages that proliferate abnormally and secrete immunoglobulins. Peripheral nerve myelin sheaths are composed of a variety of glycolipids and glycoproteins, of which sphingolipids and myelin-associated proteins (MAGs) are thought to be the antigens associated with immune-mediated peripheral neuropathies.
Symptoms
Two sets of clinical signs and symptoms are present, namely, manifestations of multisystemic lesions due to monoclonal gammopathy and manifestations of peripheral motor and sensory autonomic dysfunction due to peripheral nerve damage. This is one of the clinical features of the disease.
MGUS or benign monoclonal gammopathy combined with peripheral neuropathy is mainly seen in patients over 50 years of age, with insidious onset, and symmetrical polyneuropathy is common, mainly manifested as numbness of the feet, sensory abnormalities, balance disorders, and gait instability, with deep sensory and tactile sensory involvement, and other deep sensory involvement, and half of the patients have pain and discomfort. The course of the disease often extends for several years to decades, and in the late stage, there are symptoms of motor nerve involvement, such as weakness and atrophy of the distal lower limbs to varying degrees, but it is rare for muscle weakness to lead to bed-ridden. A few patients may present with simple motor neuropathy, which is quite similar to motor neuron disease.
Examination
1. Laboratory tests
(1) Protein electrophoresis of serum Protein electrophoresis and immunoelectrophoresis of serum should be routinely performed in idiopathic peripheral neuropathy of undetermined cause to detect the presence or absence of M protein.
(2) Urinary peripheral protein Sometimes, although serum M protein is negative, the light chain of M protein can enter the urine called peripheral protein. Urinary peripheral protein has the same clinical significance as serum M protein, so the urine test must be performed at the same time as serum.
(3) Cerebrospinal fluid protein is often increased.
(4) Bone marrow aspiration may show increased plasma cells, which may be heterogeneous or naïve.
2. Other auxiliary tests
(1) Electrophysiological examination: Electromyography shows symmetrical slowing of distal conduction velocity of peripheral nerves, with sensory involvement, prolongation of distal motor latency, and in severe cases, conduction block and waveform dispersion can be seen, and waveform amplitude can be seen to decrease, i.e., there is axonal involvement.
(2) Related tests: monoclonal gammaglobulin, urinary aggrecan, cerebrospinal fluid.
Diagnosis
1. Clinical manifestations of peripheral neuropathy such as sensory and motor deficits.
2. Protein electrophoresis and immunoelectrophoresis of urine and serum should be routinely performed to detect the presence or absence of M-protein in idiopathic peripheral neuropathy of unknown cause.
3. Cerebrospinal fluid protein is often increased.
4. Electrophysiologic examination may show limited motor conduction block.
5. Segmental demyelination or axonal degeneration may be seen on peroneal nerve biopsy if necessary.
Differential diagnosis
The relationship between monoclonal gammopathy peripheral neuropathy and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy cannot be determined at this time.The clinical presentation and electrophysiologic features of CIDP are very similar to those of certain types of monoclonal gammopathy peripheral neuropathy and all have elevated cerebrospinal fluid proteins, which can be comorbid with monoclonal gammopathy in 1/4 of the cases of CIDP.20% to 84% of patients with multifocal motor neuropathy have detectable antibodies to GM1 in their serum, of which 20% are monoclonal and the rest are polyclonal. It is hypothesized that CIDP and multifocal motor neuropathy may share a common pathophysiologic mechanism with monoclonal gammopathy peripheral neuropathy.
Treatment
1. Treatment of malignant monoclonal gammopathy peripheral neuropathy.
2. In benign monoclonal gammopathy, patients with IgG and IgA type M proteins respond effectively to high-dose immunoglobulin therapy, with improvement in symptoms after several days or weeks of administration.
3. Plasma exchange, steroids, and other immunosuppressive treatments can also be effective. Immunoabsorption can remove IgG antibodies and complement from the blood, but may cause a transient exacerbation of the disease and must be performed once a month.
4. IgM-type benign monoclonal gammopathy is poorly treated by immunosuppressive drugs, and clinical improvement can only be achieved after the M protein has been reduced to a certain level by applying a sufficient amount of cyclophosphamide or chloroquine.