Journal of Pain and Symptom Management
Volume 38, Issue 5 , Pages e3-e5, November 2009

Axonal Common Peroneal Nerve Palsy and Delayed Proximal Motor Radial Conduction Block Following Infliximab Treatment

Department of Neurology, Saint Andrew's State General Hospital, Patras, Greece

Article Outline

 

To the Editor:

A 38-year-old female, treated with infliximab (3mg/kg) for a two-year history of psoriatic arthritis, was referred with a sudden onset of left foot drop. At referral, eight courses of infliximab (anti-tumor necrosis factor [anti-TNF] monoclonal antibody) had already been infused. Her past medical history was otherwise unremarkable. No familial history of hereditary neuropathies, that is, hereditary neuropathy with liability to pressure palsy, was reported.

Examination revealed paresis of the left tibialis anterior, peroneous longus and extensor hallucis longus (Medical Research Council [MRC] Scale for Muscle Strength:4/5). Sensory function, tendon reflexes, and also a lumbar spine magnetic resonance imaging (MRI) scan were normal. The findings of the nerve conduction study (stimulation sites at the ankle, at distal, and proximal to fibular head) were consistent with left axonal common peroneal nerve palsy, characterized by small peroneal compound motor action potentials (CMAPs) from the extensor digitorum brevis and tibialis anterior. Peroneal CMAPs and the superficial peroneal response were <50% compared to the contralateral side. There was no evidence of conduction block around the fibular head. Sural and saphenous nerve sensory conduction study was normal. Needle electromyography (EMG) showed mildly reduced recruitment of motor units in the affected peroneal nerve-innervated muscles and in the short head of the biceps femoris. Overall, and considering that, according to the patient's statement, there was no evidence of peroneal nerve mechanical irritation from prolonged leg crossing or squatting, the neurophysiological findings were considered to be nonlocalizing.1

Blood counts, general biochemistry, protein electrophoresis, tumor markers, rheumatoid factor, serum cryoglobulin levels, and antinuclear antibodies (ANA) were either normal or negative. Erythrocyte sedimentation rate was 28mm/hour. Use of the Naranjo adverse drug reaction probability score2 revealed a probable relationship between infliximab and neurotoxicity. Therefore, infliximab was replaced by methotrexate, resulting in a progressive resolution of symptoms.

Three months after infliximab dechallenge, she was again referred with right hand drop. Examination revealed paresis of the right extensor carpi radialis, extensor digitorum communis (MRC:2+/5), and triceps (MRC:3+/5). Nerve conduction study revealed a partial motor conduction block of the right radial nerve at the Erb's point. The radial sensory study was normal. EMG in right radial nerve-innervating muscles showed decreased recruitment and early motor unit potential remodeling. Residual left axonal common peroneal nerve palsy also was evident. Laboratory analyses were similar as before, apart from an increased titer of ANA (1:320). Cerebrospinal fluid assay, and a brain and cervical spine MRI were unremarkable.

Three months afterward, and while the patient had been left untreated with observation alone, a spontaneous improvement was observed. The left peroneal nerve function was normal and the radial nerve conduction block significantly decreased. EMG in radial nerve-innervated muscles showed a mildly decreased recruitment.

She was then treated with intravenous immunoglobulin G (IVIG) (24mg/day) for three days. A month afterward, there was a marked increase in the muscle strength of the right hand. The nerve conduction study was normal.

The literature contains several cases of complex regional pain syndrome3 and immune-mediated neuropathies secondary to anti-TNF-α therapy, including multifocal motor neuropathy,4, 5, 6 sensorimotor axonopathies,4, 5, 6 chronic inflammatory demyelinating polyneuropathies,7 mononeuritis multiplex,8 and Lewis-Sumner syndrome.9 In our case, the clinical, laboratory and electrophysiological findings rule out these diagnoses.

The onset of manifestation of neurotoxicity after infliximab administration (16 months) corresponds to that previously reported.10 However, our case differs in that the radial nerve conduction block occurred three months after infliximab cessation and while the peroneal nerve function started to resolve. Bearing in mind the elevated ANA titers at that time, the delayed genesis of conduction block could be explained by the delay in anti-TNF-related induction of autoantibodies. Induction of autoantibodies, usually appears six weeks following infliximab administration and peaks as early as three to six months afterward.11 To our knowledge, our case is the first to describe delayed manifestation of conduction block after infliximab discontinuation.

Our patient experienced a gradual improvement with observation alone, and a marked recovery after the IVIG administration. However, this improvement over a short time is consistent with a mechanism of ischemia reversed from infliximab withdrawal rather than with IVIG.8

Sequential EMG studies failed to document evolution of axonal changes, thereby supporting the demyelinating background of the radial nerve conduction block. This is further supported by the relatively rapid improvement, an unlikely event in axonopathies. Overall, this lesion is attributed to infliximab-triggered autoimmune or ischemic mechanism. Considering the rapid recovery of peroneal nerve function after dechallenge, the pathogenesis of this lesion is difficult to explain. Nevertheless, electrophysiological features were consistent with an axonal lesion of the peroneal branch of the sciatic nerve, possibly because of infliximab-induced inhibition of signaling support of axons.10 It seems that this lesion represents a separate entity than the subsequent manifestation of radial nerve conduction block.

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References 

  1. Aprile I, Caliandro P, La Torre G, et al. Multicenter study of peroneal mononeuropathy: clinical, neurophysiologic, and quality of life assessment. J Peripher Nerv Syst. 2005;10:259–268
  2. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–245
  3. Chahine LM, Patrick R, Tavee J. Complex regional pain syndrome after infliximab infusion. J Pain Symptom Manage. 2008;36:e2–e4
  4. Jarand J, Zochodne DW, Martin LO, Voll C. Neurological complications of infliximab. J Rheumatol. 2006;33:1018–1020
  5. Singer OC, Otto B, Steinmetz H, Ziemann U. Acute neuropathy with multiple conduction blocks after TNF-alpha monoclonal antibody therapy [Letter]. Neurology. 2004;63:1754
  6. Tektonidou MG, Serelis J, Skopouli FN. Peripheral neuropathy in two patients with rheumatoid arthritis receiving infliximab treatment. Clin Rheumatol. 2007;26:258–260
  7. Richez C, Blanco P, Lagueny A, Schaeverbeke T, Dehais J. Neuropathy resembling CIDP in patients receiving tumor necrosis factor-a blockers. Neurology. 2005;64:1468–1470
  8. Jarrett SJ, Cunnane G, Conaghan PG, et al. Anti-tumor necrosis factor-alpha therapy-induced vasculitis: case series. J Rheumatol. 2003;30:2287–2291
  9. Hooper DR, Tarnopolsky MA, Baker SK. Lewis-Sumner syndrome associated with infliximab therapy in rheumatoid arthritis. Muscle Nerve. 2008;38:1318–1325
  10. Stübgen JP. Tumor necrosis factor-alpha antagonists and neuropathy. Muscle Nerve. 2008;37:281–292
  11. Allanore Y, Sellam J, Batteux F, et al. Induction of autoantibodies in refractory rheumatoid arthritis treated by infliximab. Clin Exp Rheumatol. 2004;22:756–758

PII: S0885-3924(09)00742-8

doi:10.1016/j.jpainsymman.2009.06.006

Journal of Pain and Symptom Management
Volume 38, Issue 5 , Pages e3-e5, November 2009

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