Demyelinating Disease following Anti-TNFa Treatment: A Causal or Coincidental Association? Report of Four Cases and Review of the Literature

Abstract

Tumor necrosis factor antagonists (anti-TNFa) are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported and literature data suggest a potential role of anti-TNFa in the induction of demyelination of the CNS. We present four patients treated with anti-TNFa who developed symptoms suggestive of CNS demyelination. The first patient, a 17-year-old male who received etanercept for psoriatic arthritis for eight months, presented with dysesthesias up to T4 level. The second patient, a 30-year-old male treated with adalimumab for three years due to ankylosing spondylitis, presented with right unilateral tinnitus. The third case, a 47-year-old female, received etanercept for four years because of psoriatic arthritis and developed persistent headache and left-sided face and head numbness. Finally, the fourth patient, a 57-years-old female treated with etanercept for six years due to ankylosing spondylitis, presented with difficulty in speech, swallowing, and ptosis of the right corner of the mouth. In all cases, brain MRI showed lesions suggestive of demyelination, while positive oligoclonal bands were detected in the CSF. Anti-TNFa treatments were discontinued and patients showed clinical improvement with pulsed intravenous corticosteroid therapy. CNS demyelination following anti-TNFa treatment represents a relatively rare but potential serious complication. Close follow-up and MRI monitoring of these patients is mandatory to elucidate whether the clinical manifestations represent adverse events occurring during anti-TNFa therapy or a first demyelinating episode.

Figure 1

(a) and (b): Axial FLAIR brain MRI of the first patient demonstrating right subcortical and juxtacortical and left periventricular hyperintense lesions (black arrows). (c) Coronal FLAIR brain MRI showing a left periventricular hyperintense lesion (dotted black arrow). (d) Sagittal T2-weighted MRI of the cervical spine showing hyperintense lesions on C3 and C4-C5 level (black arrowheads). (e) The lesion on C3 level appears to be enhanced on T1-weighted image (black arrowhead). (f) Sagittal T2-weighted MRI of the thorasic spine demonstrating a hyperintense lesion on T11 level (black arrowhead).

Figure 2

(a) Axial T2- and (b) T1-weighted brain MRI of the second patient showing subcortical hyperintense lesions, one with contrast enhancement (black arrows). (d) and (e) Sagittal T1 weighted with gadolinium brain MRI images showing enhanced corpus callosum lesions (black arrows). (c) Sagittal and (f) axial T2-weighted cervical spine MRI showing one hyperintense lesion (red arrows) on level C7-T1.

Figure 3

(a) and (b) Axial FLAIR brain MRI images of the third patient demonstrating multiple periventricular and subcortical lesions at the parietal and temporal lobes (white arrows). (c) and (d) Sagittal T2-weighted brain MRI images showing multiple lesions of the corpus callosum (black arrows).

Figure 4

(a) and (b) Axial FLAIR brain MRI images of the fourth patient demonstrating multiple periventricular and subcortical lesions at the frontal, parietal, and temporal lobes (black arrows). (c) Axial T1-weighted brain MRI image showing gadolinium ring enhancement in one of the subcortical lesions (white arrow) and two subcortical black holes (white dotted arrows) (e) Sagittal T2- and (f) T1-weighted MRI of the cervical spine showing one hyperintense lesion at the C4-C5 level with gadolinium enhancement (white arrowheads).