Infliximab-associated neuropathy in RA patients--the importance of considering the diagnosis of mononeuritis multiplex.

Accurate recognition of demyelinating syndromes affecting the peripheral and central nervous system is increasingly important in rheumatoid arthritis (RA) patients, given the association of TNF-alpha inhibitors with multiple sclerosis and demyelinating neuropathies. Tektonidou et al. report on two patients with RA developing neuropathy during treatment with Infliximab, including a patient with electrodiagnostic features reportedly consistent with a diagnosis of multifocal motor neuropathy with conduction block (MMNCB) [1]. However, there are several clinical and electrodiagnostic features of this patient’s neuropathy, which are potentially more consistent with an axonal mononeuritis multiplex. First, MMNCB is a diagnostic entity characterized by the insidious progression of asymmetric motor neuropathy developing over months to years, with reports of symptoms persisting for decades before diagnosis [2]. The chronicity of lower motor signs, such as wasting and fasciculation, can be confused with ALS. Therefore, the relative acuity of asymmetric motor neuropathy with rapid deterioration after an Infiximab infusion is highly atypical of MMNCB. In a case report referenced by the authors, Singer et al. describe a multifocal neuropathy with conduction blocks developing over 3 weeks in a RA patient treated with Infliximab. In this report, Singer et al. carefully note that the acuity of neuropathic symptoms, coupled with overlapping axonal electrodiagnostic features, necessitated a diagnosis other than MMNCB [3]. In another case report putatively describing MMNCB in a RA patient treated with Infliximab, the presence of cryoglobulins imply that the salient neuropathic mechanism might be a cryoglobulinemic vasculitis [4]. It is important to appreciate that “conduction block” is an electrodiagnostic term, which is not synonymous with demyelinating neuropathies, but can also be found in the axonal neuropathy of mononeuritis multiplex [5, 6]. The conduction block of mononeuritis multiplex is usually transient, occurring at focal regions of axonal ischemia. Over time, the conduction block disappears, and is replaced by electrodiagnostic features of an axonal neuropathy— leading to its designation as a “pseudo-conduction block” [5, 6]. Therefore, in the current patient, the multifocal regions of distal weakness, which presumably correspond electrodiagnostically to multiple conduction blocks, could also have a vasculitic as well as a demyelinative etiology. Sequential EMGs are useful to determine whether a conduction block is due to a demyelinating or an axonal neuropathy. In the authors’ case, if followup EMGs showed evolution of axonal changes, —i.e., decrease in amplitude of distal compound motor action potentials (CMAP) on nerve conduction studies, or evolution of fibrillations in denervated muscles—then this would be more suggestive of an axonal mononeuritis multiplex with a “pseudo-conduction block”. Although, neither specific nor necessary for diagnosis of MMNCB, the anti-GM1 antibody is associated with MMNCB in approximately 50% of cases [2], and would further have been useful in distinguishing between a demyelinating Clin Rheumatol (2007) 26:281–282 DOI 10.1007/s10067-006-0436-6