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Paraproteinaemic polyneuropathies are usually chronic and respond poorly to treatment.1 An exception to this is seen in the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes),2 in which polyneuropathy may improve after treatment for the osteosclerotic myeloma with which it is often associated. Progressive paraproteinaemic neuropathies may also be associated with multiple myeloma, Waldenstrom’s macroglobulinaemia, monoclonal gammopathy of undetermined significance, amyloidosis, and Castleman’s disease.3 Monoclonal gammopathy is often detected in patients with chronic lymphocytic leukaemia,4 but the association between paraproteinaemic polyneuropathy and chronic lymphocytic leukaemia has not previously been reported.
A 73 year old woman with diet controlled diabetes developed, over three days, progressive, bilateral leg weakness without sensory disturbance or sphincter symptoms. Examination disclosed a profound flaccid leg weakness with areflexia and flexor plantar responses. There was a partial right third cranial nerve palsy and poor adduction of the left eye, which improved spontaneously within two weeks of admission. The spleen tip was palpable, but there was no hepatomegaly or lymphadenopathy. Investigations included a white blood cell count of 160 × 109/l, platelets 90 × 109/l with normal haemoglobin, electrolytes, and liver function. An IgG κ-paraprotein band (33 g/l) was detected on protein electrophoresis. Morphology and immunophenotyping of the white cells in peripheral blood and bone marrow were diagnostic of chronic lymphocytic leukaemia. MRI of the brain and thoracolumbar spine was normal. Total protein in CSF was 1.3 g/l (normal 0.3–0.6 g/l) and glucose was 3.4 mmol/l (plasma 4.7 mmol/l). No atypical lymphocytes were seen on a centrifuged specimen. Nerve conduction studies performed 10 days after admission showed absent sural nerve sensory action potential and distal slowing of motor conduction in both upper and lower limbs (ulnar nerve distal motor latency 4.7 ms and conduction velocity 46 m/s; common peroneal nerve distal motor latency 8.5 ms and conduction velocity 34 m/s). Ulnar nerve F response was 33.6 ms and no F responses were detected from common peroneal nerve stimulation. No antibodies against myelin associated glycoprotein were detected in the serum. A diagnosis of postinfectious acute inflammatory demyelinating polyradiculopathy (AIDP) prompted treatment with intravenous immunoglobulin. After six weeks without improvement treatment with 60 mg prednisolone daily was started. A sural nerve biopsy showed severe loss of large and small myelinated fibres, but no malignant infiltration or deposition of amyloid light chains or cryoglobulin. After 10 weeks without clinical improvement and still wheelchair bound, treatment with 10 mg chlorambucil daily was started. Within a week of this treatment she could lift her legs off the bed. After six cycles of combined treatment (two weeks 10 mg chlorambucil, 40 mg prednisolone daily, followed by two weeks off treatment) she was able to walk with a stick. Her white cell count had fallen to 8 × 109/l (46% lymphocytes) and her paraprotein to 8 g/l.
Chronic lymphocytic leukaemia is the most common human leukaemia but infrequently causes neurological symptoms. The predominant neurological complications of chronic lymphocytic leukaemia are due to meningeal5 or peripheral nerve infiltration,6both of which were excluded in our patient. Although rare cases of axonal peripheral neuropathy have been described in patients with chronic lymphocytic leukaemia,6 we think that this is the first case of a paraproteinaemic demyelinating polyneuropathy associated with chronic lymphocytic leukaemia. This case is not typical of the POEMS syndrome in that the neuropathy was of relatively acute onset, there was no endocrinopathy or skin changes and, in POEMS, the underlying haematological disorder is usually osteosclerotic myeloma. An autoimmune aetiology of the polyneuropathy seems likely as quantitative defects of the immunoglobulins in chronic lymphocytic leukaemia can disrupt the anti-idiotype network’s regulation, resulting in autoimmune manifestations that may affect peripheral nerves. In addition, peripheral demyelination may be caused by binding of the paraprotein and complement C3b to myelin associated glycoproteins.7 It is of interest that specific treatment of the lymphoproliferative condition in our patient resulted in a reduction in the paraprotein and a dramatic clinical improvement.
This case emphasises the diversity of haematological malignancies that can manifest as paraproteinaemic demyelinating polyneuropathy. The prognosis for neuropathies associated with paraproteinaemia is generally poor, but this case suggests that chronic lymphocytic leukaemia, in addition to POEMS, is an example in which treatment of the underlying disorder may modify the natural history of the neuropathy.
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