Early recognition of POEMS syndrome: what is the role of clinical neurophysiology?

POEMS syndrome (also known as CroweFukase syndrome) is a serious systemic disease characterised by polyneuropathy, anasarca, skin lesions and associated with ostoclastic bone lesions and with M-proteinemia. The diagnosis of POEMS syndrome is made robust by finding increased serum/plasma vascular endothelial growth factor (VEGF) in addition to the combination of the above mentioned characteristic manifestations. In fact, the recognition of POEMS syndrome has been enunciated by recent diagnostic guidelines from the western and Asian countries. From our end, a second nationwide survey of POEMS syndrome was conducted in Japan in 2004. The estimated number of affected individuals all over Japan was calculated to be around 340. While the recent remarkable progress in the treatment strategy enables one to attain a remarkable clinical improvement from this serious condition, the prognosis of POEMS syndrome mostly depends on the duration from the disease onset to arriving at a precise diagnosis. The diagnosis of advanced POEMS syndrome is not difficult when the combinations of characteristic manifestations are fulfilled. However, in the initial stages, only half of POEMS patients start with neuropathy. Neuropathy in POEMS syndrome is characterised by a subacute, progressive sensorimotor type of polyneuropathy with mixed features of demyelination and axonal degeneration. The progressive muscle weakness and eventual atrophy undoubtedly causes a disabling disease that impinges on one’s quality of daily life. Electrophysiological studies contribute to a neurologist’s high suspicion of POEMS syndrome, which now directs one to a systematic physical and laboratory examination, including testing for elevated VEGF. However, nerve conduction study (NCS) results of POEMS syndrome occasionally fulfil the electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), thus leading to the caveat of an often initial misdiagnosis of CIDP. The NCS results from two large cohorts of POEMS patients were compared with CIDP. 4 Both results are almost identical with respect to the following characteristic findings in POEMS syndrome: (1) more uniform slowing of nerve conductions; (2) rare conduction blocks and temporal dispersion; (3) greater axonal loss in the lower extremities; and (4) high terminal latency index (TLI). TLI represents the comparison between intermediate and distal nerve segment latencies. If one were to use the TLI in the median nerve to distinguish POEMS syndrome from CIDP, the test sensitivities are 70% and 93%, and test specificities are 77% and 62%, respectively. These NCS differences may be due to the different pathophysiology of the two diseases. CIDP is mainly brought about by an immune-mediated mechanism, in that autoimmune mechanism including antibodies against the peripheral nerve components, such as anti-sulphated glucuronyl paragloboside antibody, directly damage nerves. On the other hand, in POEMS syndromes, antibodies directed against the nerve have not been found. The contribution of an elevated VEGF in the pathophysiology of POEMS may be hinged on the propensity for the breakdown of the blood-nerve barrier, and on the increase of metalloproteinases and tissue inhibitor of metalloproteinases that may induce nerve damages. To another extent, VEGF also has effects on the microangiopathy and on the Schwann cell function. While details of the pathophysiology of polyneuropathy in POEMS syndrome remain wanting, the above mentioned mechanisms potentially induce diffuse demyelination and axonal degeneration along the nerves, which are now detected by clinical electrophysiology.