Multifocal deficits due to leukemic meningoradiculitis in chronic lymphocytic leukemia

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Abstract

Symptomatic nervous system leukemic infiltration is rarely observed in CLL. Various clinical manifestations including headache, confusion, cranial nerve palsies, focal central deficits and peripheral neuropathies have been seldom reported, occurring in less than 1% of patients.

We report herein 2 CLL patients with unusual clinical presentations of nervous system invasion. They presented multiple progressive peripheral deficits due to meningoradiculitis. In both, CSF immunophenotyping analysis identified a majority of T cells (> 90%), and less than 10% of B-CLL cells expressing CD5, CD19 and CD20. Our analyses revealed the transformation of CLL into an aggressive B-cell lymphoma in one case (Richter's syndrome). A post mortem study showed massive infiltration of cranial nerves and spinal roots by large B lymphomatous cells. In the other case, CNS oriented chemotherapy led to remission and total neurological recovery.

In practice, the etiological diagnosis of neurological deficits in CLL patients is difficult. CSF analysis may be useful, requiring viral PCR, repeated cytological studies and immunophenotyping analysis. Although rare, leptomeningeal leukemic localization has to be discussed, even in the absence of overt Richter syndrome, and may require an early therapeutic test.

Introduction

Chronic lymphocytic leukemia (CLL) is the most common leukemia occurring in adulthood.[1] It is an indolent malignancy of the lymphoid tissue that is characterized by the proliferation and accumulation of monoclonal B-type CD5/CD23 lymphocytes, with a frequent minimally symptomatic course for many years [1]. It principally affects the elderly, with a median age of disease of 65 year-old and 7 year average survival from the time of diagnosis. In addition to Binet or Rai clinical staging where advanced stages are associated with a poor outcome, several new prognostic factors have been recognized and also confer a worst outcome such as a doubling lymphocyte time less than 12 months, 17p- or 11q-cytogenetic deletions, ZAP 70 and CD38 expression, high serum level of thymidine kinase or unmutated mutational profile of immunoglobulin genes [1]. Several types of complications can occur, including autoimmune hematological manifestations, complications of treatments, intercurrent infections, associated solid tumours and direct effects of tumour infiltrations or clonal evolution to an aggressive B-cell lymphoma (Richter's syndrome [RS], which occurs in 3 to 15% of CLL patients) [1].

The overall symptomatic neurological complications rate in CLL is low. Although CLL is a relatively common condition, only one large clinical series describing the neurological complications in these patients has been reported. In this study, Bower et al (1997) identified 11.3% of patients with neurological complications in a series of nearly 1000 CLL patients [2]. Neurological complications included mainly herpes zoster infections (7.2%) or other opportunistic infections (1.8%; including progressive multifocal leukoencephalopathy, cryptococcal, pneumococcal, and candidal meningitis and aspergillus brain emboli), treatment-related conditions (1.5%), and exceptionally direct leukemic involvement of neural tissue (0.8%; including one with RS).

We report here 2 CLL patients presenting peculiar initial neurological manifestations associating progressive one-limb and cranial nerve palsies. These multifocal peripheral deficits revealed tumoral infiltrations and meningitis, due to a Richter transformation in one of the patients.

Section snippets

Case report 1

An 80-year-old male was admitted in October 2005 because of progressive difficulty in walking and recent confusion. He was found to have CLL in 2003 (stage B, Binet classification). Chemotherapy was initiated for one year because of high lymphocytosis (chlorambucil from February 2003 to April 2004). He developed Bell's palsy in August 2004, regressive with corticotherapy within a few weeks. In 2005, low back pain occurred in May, acute urinary retention in June and progressive walking

Discussion

In contrast to acute lymphoblastic leukaemia, in which up to 20% of the patients are at risk of CNS leukemic infiltration, CLL rarely involves the nervous system.

Concerning the central nervous system (CNS), symptomatic invasion by CLL is extremely rare. To date, less than 30 cases have been reported in the literature, with various initial clinical manifestations, including headaches, confusional state, cranial nerve abnormalities, optic neuropathy, cerebellar ataxia or spinal paraparesis, most

Conclusion

We report herein 2 CLL patients with neurological symptomatic infiltrations. In one case, this unusual clinical presentation was related to a proven Richter's syndrome transformation. In the second case, in the absence of a detected aggressive B-cell lymphoma, oriented CNS chemotherapy led to a dramatic clinical improvement and CLL remission. Our data confirmed that neurological infiltrations have to be discussed in cases of abnormal neurological symptoms in CLL patients with meningitis even in

Acknowledgment

The authors thank Michael Dubow for editing assistance.

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