Miller-Fisher syndrome associated with chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy, with meningeal or peripheral nerve infiltrations being the most commonly encountered neurological complications. In this report, we describe a CLL patient with Miller-Fisher syndrome (MFS) who responded to immune modulation with plasmapheresis. A 47-year-old man diagnosed as B-cell CLL admitted with neutropenic fever. He complained of diplopia and numbness of both arms. Neurological examination revealed a bilateral external ophthalmoplegia, dysphagia, dysarthria, mild shoulder girdle muscle weakness and gait ataxia, accompanied by absent tendon reflexes. Nerve conduction studies were indicative of a predominantly axonal sensori-motor peripheral neuropathy. This association of CLL with MFS had not been previously reported in the literature.

Lymphoma-associated dysimmune polyneuropathies

“…CSF analysis on 3 patients showed only elevated protein concentration [106,107,109]; however, "atypical", non-neoplastic lymphocytes were detected on repeat CSF evaluation in the patient with recurrent MFS [109]. Electrodiagnostic studies were variably interpreted as: (a) axonal sensory polyneuropathy [106]; (b) diffuse, predominantly axonal sensorimotor polyneuropathy [107,108], or (c) sensorimotor demyelinating polyradiculoneuropathy [109].…”

“…Three patients showed neurological response to treatment [106,108,109]; 1 treatment-unresponsive patient showed neurological improvement to systemic chemotherapy for lymphoma [107]. The patient with recurrent MFS and CSF atypical pleocytosis showed neurological improvement to a combined systemic/intrathecal chemotherapy regimen [109]; neurological response to systemic chemotherapy was interpreted as evidence of a "paraneoplastic" pathogenesis (herein defined as the production of a specific antibody against an antigen of malignant cells that crossreacts with an antigen of normal neurological tissue).…”

“…The temporal association between a diagnosis of MFS and lymphoma varied: (a) onset of MFS coincided with the 2nd relapse of lymphoma [106]; (b) MFS coincided with the discovery of lymphoma in a renal transplant recipient on anti-rejection therapy [107]; (c) MFS developed in a patient with CLL during chemotherapy [108], and (d) a detailed evaluation during recurrence of MFS detected lymphoma [109]. An elevated serum anti-GQ1b antibody titer is deemed useful supportive evidence for (?…”

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

“…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.…”

Successful Treatment of Refractory Guillain-Barré Syndrome with Alemtuzumab in a Patient with Chronic Lymphocytic Leukemia

“…Chronic lymphocytic leukemia (CLL) is associated with autoimmunity, but neurologic autoimmune phenomena have been rarely described. In our review of the literature, we identified 5 cases of GBS associated with CLL [11,12,13,14,15], 1 case of MFS [16], 1 case of a sensorimotor polyneuropathy with a positive antiganglioside antibody [17] and no cases of BBE or AO.…”