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

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 (). 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 (). 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 ().

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.

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.

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).

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 (; ). 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 (; ). 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 ().

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 (). However, predictive risk factors for early detection of CNS involvement in CLL have not been identified (). Currently, imaging findings and CSF morphology, cytometric and cytogenetics studies are used to evaluate and determine the presence of CNS involvement in CLL patients (). 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 (). 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 (). 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 (). 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.

No funding was provided for this article.