The natural history of chronic demyelinating neuropathy associated with benign IgM paraproteinaemia

Abstract

Eighteen patients are described, all of whom had chronic demyelinating peripheral neuropathy and benign IgM paraproteinaemia. All patients had serum antibodies against peripheral nerve myelin or myelin-associated glycoprotein. Seventeen were followed up clinically and electrophysiologically for between 1 and 14 years (mean 7.4 years). The presenting symptoms and signs were almost always those of a distal sensory disturbance in the limbs followed by distal weakness. All patients developed tremor or ataxia in the arms, and gait ataxia. The severity of the neuropathy varied greatly between patients at similar stages. Some had a predominantly sensory deficit and others a predominantly motor deficit. All patients eventually developed both motor and sensory signs. The neuropathy became slowly worse over the first 2-5 years and then appeared to stabilize, although long-term follow-up did reveal a very slow progression in the group as a whole. No patient developed evidence of haematological malignancy but two patients died of malignancy involving other systems. On reviewing 75 patients from the literature, non-haematological malignancy was found to be the commonest cause of death.

Cerebellar learning distinguishes inflammatory neuropathy with and without tremor

“…Neurology Inflammatory mediated neuropathies are common and potentially treatable. 1 Tremor occurs with immunoglobulin M paraproteinaemic neuropathy (IgMPN) [2][3][4] and less commonly in other inflammatory neuropathies. 5 It has been suggested that temporally distorted peripheral inputs reach a normally functioning central processor, such as the cerebellum, which is misled into producing a delayed second agonist burst and tremor.…”

Anti-MAG IgM penetration into myelinated fibers correlates with the extent of myelin widening

“…The myelin sheaths are thinner than normal, and some figures of concentric Schwann cell proliferation referred to as "onion bulbs" are seen. 20 Deposits of monoclonal IgM on the myelin sheaths 22,23 and ultrastructural alterations consisting of a widening of myelin lamellae in peripheral nerve 11,13,17 are characteristic features of the neuropathy with anti-MAG monoclonal IgM antibody. Widening of myelin lamellae is observed in more than 90% of patients with neuropathy associated with anti-MAG IgM.…”

Physiological tremor analysis of patients with anti-myelin-associated glycoprotein associated neuropathy and tremor

“…In addition, we found that the tremors found in anti-MAG associated neuropathy patients worsened significantly with action, in agreement with the findings of an earlier report. 12 The non-anti-MAG patients in our series exhibited the low-amplitude, high-frequency (8-12 Hz) symmetric, postural tremor and suppression of EMG burst pattern characteristic of EPT. The average frequency for these patients during the arms extended trial was 9.10 ± 1.09 Hz, which lies within the 8-12-Hz range of frequencies commonly seen in patients with EPT.…”

“…5 In addition, several studies have documented that tremor improves in neuropathy patients treated with high doses of prednisone, immunosuppressants, or intravenous immunoglobulin infusions, 2,4,5,7 suggesting a correlation between the tremor and the underlying neuropathy. In studies of initially 12 then expanded to 18 patients a decade later, 12,13 Smith et al observed similar findings of significant tremor and ataxia in patients with chronic demyelinating neuropathy and benign paraproteinemia.…”