Multifactorial Neuropathy

It is well known that in a small proportion of patients with peripheral neuropathy a cause is not found; on the other hand, it is also possible that extensive investigations reveal more than one possible cause of peripheral neuropathy, especially in older patients, raising a different kind of diagnostic problem. The aim of this study was to investigate the occurrence of “multifactorial neuropathy” in a population of patients with peripheral neuropathy, and the modalities of interaction when various causes are implicated in determining the features of neuropathy. In a series of 62 consecutive patients with peripheral neuropathy who underwent an extensive diagnostic work‐up, more than one possible cause for a single patient was found in 24 patients (38.7%), and at least 3 causes in 9 patients (14.5%). Common causes of neuropathy, such as diabetes, alcohol, drugs, Charcot‐Marie‐Tooth disease, and cryoglobulinemia were more often implicated in multifactorial neuropathy. In 8 additional patients, neuropathic motor and sensory impairment was complicated by coexistent diseases (Parkinson's disease, osteoarthrosis, lumbal stenosis). Patients with multifactorial neuropathy were older than patients with neuropathy due to a single cause (mean age: 66.8 ± 9.6 vs. 62.2 ± 11.9), and had a significantly greater disability on Rankin scale (28/32 with Rankin grade 2 or more, vs. 15/30; p = 0.002). Possible mechanisms of interaction between two or more causes of neuropathy are the following: a primary neuropathic condition is worsened or revealed by an additional superimposed cause; two coexisting causes concur to determine the features of neuropathy, for instance influencing respectively motor and sensory symptoms; a unique cause produces neuropathic damage through different mechanisms (this is typically the case of malignancies, and in particular lymphoma); the significance of some potential factors of neuropathic damage, such as monoclonal gammopathy, may be difficult to be ascertained, thus their role as a cause of neuropathy remains elusive. In addition, the disability due to neuropathy may be complicated by other concurrent neurologic or non‐neurologic conditions causing additional motor or sensory impairment. Thus it is also advisable to have a complete screening in patients with an obvious cause of peripheral neuropathy, as it could be made worse by another coexistent cause, and in older patients this evenience is not uncommon. This is especially important when a treatable additional cause is revealed.