A 45-year-old woman presented with lower-extremity weakness. She first noted weakness in her ankles and feet 5 months previously. The weakness progressed to involve her knees and hips, and she had been unable to walk without support for the prior 2 months.
Electrodiagnostic studies cannot always classify a neuropathy definitively into an axonal or demyelinating category; in such cases, history and examination are essential in interpreting the results.
• What is the POEMS syndrome?
The POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome is a rare paraneoplastic syndrome associated with a monoclonal plasma-cell dyscrasia. The pathophysiology of the POEMS syndrome is not fully understood, but the overproduction of proinflammatory and proangiogenic cytokines appears to play a major role in the disorder; in particular, there is marked overproduction and secretion of VEGF [vascular endothelial growth factor] by plasma cells. VEGF-induced neovascularity and microvascular permeability are postulated to cause most of the hallmark manifestations of this syndrome. Interleukin-12 is also overproduced in the POEMS syndrome and may play a role in the pathogenesis of the disorder. Sclerotic bone lesions or Castleman’s disease (a rare lymphoproliferative disorder) are present in nearly all patients with the POEMS syndrome. The disease course is chronic and progressive, with a reported median survival of 13.8 years.
• What are the diagnostic criteria for the POEMS syndrome?
The diagnosis of the POEMS syndrome requires evidence of a polyneuropathy and a monoclonal plasma-cell proliferative disorder, as well as at least one other major criterion and one minor criterion.
Morning Report Questions
Q: Can electrodiagnostic testing distinguish between POEMS syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP)?
A: A terminal latency index of 0.38 or more, indicating comparatively less distal demyelination, has good sensitivity and specificity for distinguishing the POEMS syndrome from the more common CIDP. Patients with the POEMS syndrome usually have uniform demyelination, whereas patients with CIDP tend to have multifocal demyelination that is more severe in the proximal and distal nerve segments.
Q: How is the POEMS syndrome treated?
A: Treatment for the POEMS syndrome is guided by findings from observational studies in the absence of data from randomized, controlled trials. For patients who have plasmacytoma (or plasmacytomas) without bone marrow involvement, radiation therapy to affected sites alone may be curative. However, patients with clonal plasma cells on bone marrow biopsy require treatment with systemic chemotherapy. Patients treated with glucocorticoids in conjunction with an extended course of melphalan have had symptomatic benefit (with improvement initially in fluid overload and later in neuropathy) and reduced mortality, as compared with patients treated with either glucocorticoids alone or limited courses of alkylator-based chemotherapy. Case series of patients treated with high-dose melphalan conditioning followed by autologous peripheral-blood stem-cell transplantation have had long-lasting and clinically significant improvements in symptoms and hematologic and radiologic findings and have had normalization of plasma VEGF levels, with a 5-year overall survival rate of 94%. Case series or reports have also suggested favorable outcomes with the use of thalidomide, lenalidomide, or bortezomib-based therapies in patients who are too ill to undergo stem-cell transplantation or who have disease that is refractory to other therapies.