Giannini F.1,Volpi N.2, Venturini E.1, Rossi S.1, Fimiani M.3, Cerase A.4 1Dipartimento di Neuroscienze‐Sez. Neurologia, 2Dipartimento di Scienze Biomediche, 3Istituto di Scienze Dermatologiche (Università di Siena), 4U.O. di Neuroradiologia (Azienda Ospedaliera Senese)A 67‐year‐old man suffering from Prurigo Nodularis, steroid and cyclosporine resistant, was treated with Thalidomide (Th) at a dosage of 100 mg per day. Five months later he started to complain of tinglings on his hands and feet, gradually followed by loss of sensation. Within some weeks, he developed gait disturbances. Clinical examination, performed eight months after therapy start, showed: a complete loss of vibratory and position sense in upper and lower limbs, extended to proximal segments; severe gait ataxia with corrective effects of vision; “glove and stocking” tactile and pain hypoaesthesia; normal muscle strength except for a slight weakness of feet and toes dorsiflexion; and absence of deep tendon reflexes. The findings of electrophysiological examination were: no sensory nerve action potentials on upper and lower limbs, no somatosensory evoked spinal and cortical responses; mild reduction of motor amplitude and motor conduction velocity confined to peroneal nerves only and normal motor evoked potentials by magnetic transcranial stimulation. Therapy was withdrawn. Sural nerve biopsy showed: severe axonal loss, with axonal degeneration, myelin ovoids on teased fibres, and poor evidence of regeneration; and no significant inflammatory changes. MR imaging of the spinal cord, performed on a 1.5 T unit revealed: high intensity area in the posterior columns extending from C4‐C5 to D2 levels on T2‐weighted turbo‐spin‐echo images; no cord swelling nor gadolinium enhancement. Peripheral neurotoxicity is the main limiting adverse effect of Th, an “old” drug newly used in a wide spectrum of immune and neoplastic diseases. Th‐induced nervous impairment is reported as a predominantly sensory axonal distal polyneuropathy. The mechanism and the primary target of toxicity are so far not identified. Indeed, distal axons have been commonly considered the site of primary involvement, but Th activity on dorsal root ganglion cells is also experimentally documented. Studies on teratogenic effects show ultrastructural changes on fetal ganglion cells, temporally preceding limb malformations. Nevertheless, to our knowledge, a clinical and MRI involvement of dorsal columns, concomitant with a severe sensory axonal peripheral neuropathy due to Th, has not yet been described in humans.