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An uncommon neurological manifestation of chronic lymphocytic leukemia: Longitudinally extensive transverse myelitis

Published:October 22, 2019DOI:https://doi.org/10.1016/j.msard.2019.101455

      Highlights

      • This is a single case report of LETM during the initial phase of CLL.
      • Neurological involvement in CLL is very rare.
      • Diagnosis of CNS involvement in CLL is difficult, due to heterogeneous presentation.
      • Prognosis in CNS involvement is related to the natural history of CLL .

      Abstract

      We describe a 50-year-old male patient who was admitted to the emergency department with complaints of fever and fatigue that had suddenly started two weeks ago. In the laboratory evaluation, a white blood cell count of 131.000/mm3 was detected. The patient was hospitalized and developed fecal incontinence on the first day of hospitalization. Detailed neurological examination revealed the patient had tetraparesis. Long segment high signal intensity was observed on spinal MRI. Flow cytometry examination of the CSF and biopsy findings of the bone marrow were compatible with Chronic Lymphocytic Leukemia (CLL). The patient's MRI appearances resolved after treatment. The tetraparesis resolved partially. There was no motor deficit in upper extremities and the patient was able to walk without aid or rest for 100 m. Clinical manifestation of central nervous system (CNS) involvement in CLL is heterogeneous and therefore may be difficult to pinpoint. We have described an uncommon occurrence of CNS involvement in CLL.

      Keywords

      1. Introduction

      Chronic lymphocytic leukemia (CLL) is a disease in which B lymphocytes demonstrate clonal proliferation and accumulation in the bone marrow, circulation and lymphoid tissues. It is also known to be characteristically associated with cellular and humoral responses (
      • Szczepanek D.
      • Wasik-Szczepanek E.
      • Szymczyk A.
      • et al.
      Central nervous involvement by chronic lymphocytic leukaemia.
      ). CLL is the most common type of leukemia in adults; however, it is rare to see involvement of the central nervous system (CNS) in these patients (
      • Hanse M.C.
      • Van't Veer M.B.
      • van Lom K.
      • et al.
      Incidence of central nervous system involvement in chronic lymphocytic leukemia and outcome to treatment.
      ). The prevalence of CNS involvement in CLL has been reported to be around 0,8% in a recent study . Even so, studies involving autopsy evaluations have suggested that the prevalence of CNS involvement is actually much higher than the rates reported in antemortem studies (
      • Strati P.
      • Uhm J.H.
      • Kaufmann T.J.
      • et al.
      Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.
      ).
      Transverse myelitis is an inflammatory disease of the medulla spinalis. It is defined as longitudinally extensive transverse myelitis (LETM) if it extends to three or more vertebral segments. In this article, we present a case of CLL with longitudinally extensive transverse myelitis in order to draw attention to the occurrence of this type of CNS involvement in CLL.

      2. Case report

      A 50-year-old male patient was admitted to the emergency department with complaints of fever and fatigue that had suddenly started two weeks prior to emergency admittance. On the physical examination of the patient, there were no features other than high fever (38.5 °C). In the laboratory evaluation, a white blood cell (WBC) count of 131.000/mm3 was detected and the patient was admitted to the internal medicine clinic for further examination and treatment with a preliminary diagnosis of CLL. The only significant feature of the patient's medical history was the presence of diabetes mellitus. The patient developed fecal incontinence on the first day of hospitalization. Detailed neurological examination revealed the presence of tetraparesis. Deep tendon reflexes were decreased in the upper limbs and absent in the lower limbs. Cranial magnetic resonance imaging (MRI) was normal; whereas cervical and thoracic MRI results revealed hyperintense lesions in the T1 and T2 sections at all levels from the bulbus to the T4 vertebra corpus, which were more prominent in the C2–C3 segment (Fig. 1a and b). These lesions showed heterogeneous enhancement of contrast. The results of standard cerebrospinal fluid (CSF) laboratory investigations were as follows: glucose: 93.7 mg/dl, protein: 357.69 mg/dl, LDH: 62 U/L, Chloride: 120 mmol/L, leukocyte count: 30/mm3, and no red blood cell. There was no proliferation in CSF cultures and ARB, M.tuberculosis PCR and HSV DNA PCR were negative. The aquaporin-4 antibody detected in neuromyelitis optica was negative. Brucella and borrelia antibodies were negative. Vasculitis markers were negative. CD19, CD5, CD23, CD20 and CD22 positivity were detected on the CSF flow cytometry examination and the findings were compatible with CLL.
      Fig. 1
      Fig. 1T2 weighted sagittal MRI spine shows long segment diffuse hyperintensity extending from the bulbus to the T4 level.
      Fig. 1
      Fig. 1T2 weighted sagittal MRI spine shows long segment diffuse hyperintensity extending from the bulbus to the T4 level.
      The bone marrow biopsy of the patient showed 95% lymphoid infiltration. After the biopsy result was obtained, treatment for CLL with rituximab and cyclophosphamide was initiated. Pulse steroid treatment was planned for myelitis; however, prednisolone 100 mg/day was started because of the persistence of fever. Prednisolone was discontinued on the first day because a lung infection was detected and plasmapheresis was applied five times on alternate days. IVIG treatment was given for 5 days at a dose of 0,2 g/kg for both CLL and transverse myelitis. In the neurological examination of the patient who also received second course chemotherapy before discharge, there was no motor deficit in upper extremities and the patient was able to walk without aid or rest for 100 m. Complete regression was observed in the control cervical and thoracic MRI of the patient (Fig. 2).
      Fig. 2
      Fig. 2Complete regression of spinal cord hyperintensity.

      3. Discussion

      When we reviewed the literature on this topic, we found that only two cases with CLL and LETM comorbidity were reported. In one of these cases, transverse myelitis was identified 2 months after diagnosis and EBV was found to be positive on CSF PCR, while the other case reportedly had optic neuritis and recurrent myelitis after 5 years of CLL diagnosis (
      • Rossi C.
      • Brisou G.
      • Baseggio L.
      • et al.
      Central nervous system involvement in chronic lymphocytic leukemia: uncommon manifestation with unde?ned therapeutic management.
      ;
      • Witton L.
      • Menon S.
      • Perera S.
      A rare case of CNS involvement with Chronic Lymphocytic Leukemia CLL.
      ). The most prominent difference of our case is the fact that CLL and transverse myelitis were diagnosed at the same time and during the initial hospitalization of the patient. There a few cases in the literature that report rare but significant CNS findings of CLL, such as leptomeningeal and cavernous sinus involvement (
      • Nambiar R.
      • Nair S.G.
      Cavernous sinus syndrome.
      ;
      • Rojas-Hernandez C.M.
      • Nemunaitis J.
      • Marjon K.D.
      • et al.
      Chronic lymphocytic leukemia with clinical debut as neurological involvement: a rare phenomenon and the need for better predictive markers.
      ). In addition, a recent case of a patient with CLL that presented with progressive weakness in the lower extremity and urinary incontinence reported that the patient's spinal MRI had revealed oedema at the C2–T1 level (
      • Moazzam A.A.
      • Drappatz J.
      • Kim R.Y.
      • et al.
      Chronic lymphocytic leukemia with central nervous system involvement: report of two cases with a comprehensive literature review.
      ).
      Early diagnosis of CNS involvement and detection of risk factors for patients who develop CNS problems are crucial to the diagnosis and treatment of such conditions (
      • Moazzam A.A.
      • Drappatz J.
      • Kim R.Y.
      • et al.
      Chronic lymphocytic leukemia with central nervous system involvement: report of two cases with a comprehensive literature review.
      ). However, predictive risk factors for early detection of CNS involvement in CLL have not been identified (
      • Cramer S.C.
      • Glaspy J.A.
      • Efird J.T.
      • et al.
      Chronic lymphocytic leukemia and the central nervous system: a clinical and pathological study.
      ). Currently, imaging findings and CSF morphology, cytometric and cytogenetics studies are used to evaluate and determine the presence of CNS involvement in CLL patients (
      • Lange C.P.
      • Brouwer R.E.
      • Brooimans R.
      • et al.
      Leptomeningeal disease in chronic lymphocytic leukemia.
      ). In our patient with a LETM appearance in spinal MR, we excluded auto-immune, inflammatory, infectious, vascular and metabolic causes that would explain this condition. Biologic features of the disease are very important both in terms of prognostic markers and response to treatment CD49d and CD82 expression profiles are thought to be potential biomarkers to predict CNS involvement in patients with CLL (
      • Rojas-Hernandez C.M.
      • Nemunaitis J.
      • Marjon K.D.
      • et al.
      Chronic lymphocytic leukemia with clinical debut as neurological involvement: a rare phenomenon and the need for better predictive markers.
      ). In our case, we detected CD19, CD5, CD23, CD20 and CD22 positivity in CSF compatible with CLL.
      When looking at the prognosis of the disease, the average time of survey from the onset of neurological symptoms to death in CLL is reportedly 12 months (
      • Moazzam A.A.
      • Drappatz J.
      • Kim R.Y.
      • et al.
      Chronic lymphocytic leukemia with central nervous system involvement: report of two cases with a comprehensive literature review.
      ). In CLL patients with CNS involvement, prognosis is thought to be related to the natural history of CLL rather than to the localization of CNS involvement (
      • Lange C.P.
      • Brouwer R.E.
      • Brooimans R.
      • et al.
      Leptomeningeal disease in chronic lymphocytic leukemia.
      ). In our case, improvement was detected in the findings approximately 6 months after diagnosis.
      Neurologic involvement in CLL is rare. It is important to evaluate the neurological symptoms and signs during the course of the disease, including the stage at diagnosis. In addition to the importance of early diagnosis and clinical findings at diagnosis, both imaging and CSF examinations play a key role in the initiation of appropriate treatment for patients with CLL in the presence of CNS involvement.

      Funding sources

      No funding was provided for this article.

      Declaration of Competing Interest

      The authors declare that there is no conflict of interest.

      References

        • Cramer S.C.
        • Glaspy J.A.
        • Efird J.T.
        • et al.
        Chronic lymphocytic leukemia and the central nervous system: a clinical and pathological study.
        Neurology. 1996; 46: 19-25
        • Hanse M.C.
        • Van't Veer M.B.
        • van Lom K.
        • et al.
        Incidence of central nervous system involvement in chronic lymphocytic leukemia and outcome to treatment.
        J. Neurol. 2008; 255: 828-830
        • Lange C.P.
        • Brouwer R.E.
        • Brooimans R.
        • et al.
        Leptomeningeal disease in chronic lymphocytic leukemia.
        Clin. Neurol. Neurosurg. 2007; 109: 896-901
        • Moazzam A.A.
        • Drappatz J.
        • Kim R.Y.
        • et al.
        Chronic lymphocytic leukemia with central nervous system involvement: report of two cases with a comprehensive literature review.
        J Neuro.-Oncol. 2012; 106: 185-200
        • Nambiar R.
        • Nair S.G.
        Cavernous sinus syndrome.
        Bayl. Univ. Med. Cent. 2017; 30: 455-456
        • Rojas-Hernandez C.M.
        • Nemunaitis J.
        • Marjon K.D.
        • et al.
        Chronic lymphocytic leukemia with clinical debut as neurological involvement: a rare phenomenon and the need for better predictive markers.
        BMC Hematol. 2017; 17: 3
        • Rossi C.
        • Brisou G.
        • Baseggio L.
        • et al.
        Central nervous system involvement in chronic lymphocytic leukemia: uncommon manifestation with unde?ned therapeutic management.
        Leuk. Lymphoma. 2014; 55: 1939-1941
        • Strati P.
        • Uhm J.H.
        • Kaufmann T.J.
        • et al.
        Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.
        Haematologica. 2016; 101: 458-465
        • Szczepanek D.
        • Wasik-Szczepanek E.
        • Szymczyk A.
        • et al.
        Central nervous involvement by chronic lymphocytic leukaemia.
        Neurol. Neurochir. Polska. 2018; 52: 228-234
        • Witton L.
        • Menon S.
        • Perera S.
        A rare case of CNS involvement with Chronic Lymphocytic Leukemia CLL.
        Neurol. - AAN Enterp. 2017; (P2.217)