Rituximab responsive multiple radiculopathies and cranial nerve palsies in association with chronic lymphocytic leukaemia

Abstract

We describe a previously healthy 53 year old woman with a progressive multifocal neurological syndrome. She developed gradually progressive patchy numbness and horizontal diplopia over 3 years, night sweats and 15 kg weight loss over 1 year, and weakness of the face and four limbs over 9 months. Previous treatment for her symptoms included dual anti-platelet agents then warfarin for a positive lupus anticoagulant, oral fludarabine (50 mg for 5 days) following a diagnosis of mild chronic lymphocytic leukaemia (CLL) on bone marrow biopsy, and two courses of oral steroids (25 mg/day prednisolone; 20 mg/day dexamethosone each tapered over 4 weeks). Neurological symptoms progressed despite these treatments. On examination she mobilised with a frame. There were partial right III, VI and bilateral VII cranial nerve palsies. There was wasting of intrinsic hand muscles, distal lower limb muscles and right deltoid. There was asymmetric proximal and distal weakness in all limbs ranging from no active contraction of right deltoid, flicker of contraction of left hamstrings to mild weakness of ankle dorsiflexors. There was patchy loss of reflexes and flexor plantars. She had sensory loss to light touch and pinprick in multiple dermatomes.The working diagnosis was CLL-associated immunemediated radiculopathies and cranial neuropathies. She was treated with rituximab 375 mg/m 2 and hydrocortisone 100 mg weekly for 8 weeks without additional steroids (repeated previous steroid-associated central serous retinopathy). She made a near complete response. Three months after the rituximab her only residual symptom was with feeling a little unsteady. The only abnormalities on neurological examination were slight diplopia on right gaze and reduced vibration sensation to the ankles. Investigations (Table 1) had dramatically improved. She was maintained on oral cyclophosphamide 50 mg/day, however, had a minor relapse after 5 months and received a repeat rituximab course with good effect. She is neurologically stable on maintenance rituximab 375 mg/m 2 every 3 months.Mechanisms by which CLL could be associated with neurological symptoms include direct leukaemic infiltration, indirectly through immune-mediated effects, opportunistic infection related, treatment related or chance association. Neurological syndromes are found in 11% of CLL patients mostly relating to opportunistic infections [1]. Cases of CLL associated with GBS [2, 3], MillerFisher syndrome [4], subacute IDP [5], mononeuritis multiplex [5] and polyneuropathy [5] are reported. A case with multiple radiculopathies and cranial neuropathies was reported recently [6], however, direct leukemic infiltration of nerve roots was evident on imaging and CSF. In our patient repeated MRI and CSF examinations showed no evidence of direct leukaemic infiltration.