Although chronic lymphocytic leukemia (CLL) is very common in adults, complications associated with CLL involvement of the nervous system are very rare (1). The case report describes a CLL patient with leptomeningeal and orbital involvement. There is no standard treatment protocol for this pattern of involvement. Our patient received maintenance therapy with ibrutinib after chemoimmunotherapy, and her neurological symptoms completely resolved.

CASE: A 48-year-old female housewife was diagnosed with CLL in 2018. The 17p deletion-negative patient is being followed without treatment. She has no known history of the disease. The patient presented with complaints of decreased vision, severe headache, and double vision. Her symptoms had been present for approximately two weeks. Laboratory tests revealed WBC: 156 10e3/uL, HBG: 9.2 g/dL, platelets: 188 10e3/uL, lymphocytes: 128.41 10e3/uL, creatinine: 1.07 mg/dL, urea: 48 mg/dL, LDH: 534 U/L, sodium: 134 mmol/L, potassium: 3.38 mmol/L, and sedimentation rate: 38 mm/h. Imaging revealed a liver of 180 cm and a spleen of 180 cm. Additionally, multiple lymphadenomegaly was detected in the axillary, inguinal and neck regions.An ophthalmology consultation was performed for the patient's complaints of headache, decreased vision, and diplopia. The evaluation revealed bilateral grade 3 papilledema. Detailed cranial imaging revealed no pathology during the neurological evaluation. Cerebrospinal fluid (CSF) sampling was performed. Results for neuromyelitis optica and other neurological disorders were negative. Results for meningitis were also negative. Direct microscopic examination of the CSF revealed widespread lymphocytosis consistent with CLL. The patient's headache and visual symptoms were interpreted as CLL neurological involvement. A course of R-FC was administered. A follow-up fundus examination after the course revealed resolution of the patient's grade 3 bilateral papilledema, and her headache complaints significantly decreased. Ibrutinib was initiated as maintenance therapy and the patient was discharged for routine follow-up visits.

Conclusion: DISCUSSIONOur patient presented with neurological symptoms resulting from intraorbital and leptomeningeal disease. Leptometrial disease as the initial manifestation of CLL is extremely rare (2). A large-scale CLL autopsy study reported brain and leptomeningeal involvement in 20% and 8% of cases, respectively. This study demonstrated that CNS involvement in CLL patients is underdiagnosed. Another study revealed orbital involvement in 14 of 97 autopsies (14%) of CLL patients (3). None of the studies demonstrated a correlation between leptomeningeal spread and CLL stage or duration. Standard risk factors for CNS involvement in CLL have not been systematically investigated (4).Clinical manifestations of CNS involvement in CLL are heterogeneous and include headache, cranial nerve palsies, cerebellar findings, visual problems, and motor or sensory deficits. Imaging studies do not provide sufficient evidence of CNS involvement in CLL. The diagnosis is usually confirmed by lumbar puncture. In the present case, the CSF sample showed widespread lymphocytes. In this case, a CSF sample contaminated with peripheral blood leukocytes as a result of a traumatic lumbar puncture is unlikely, as no erythrocytes and no myeloid cells were observed in the sample. The optimal treatment for CLL patients with CNS involvement is unclear. Most such patients receive treatment that includes intrathecal chemotherapy, either with or without radiotherapy or systemic chemotherapy. The most commonly used intrathecal chemotherapy agents are methotrexate, cytarabine, and corticosteroids, used alone or in combination. Our patient is currently a high-risk patient and responded well and rapidly to chemoimmunotherapy. In general, the prognosis for patients with CLL with neurological involvement is poor. Systemic chemoimmunotherapy is the most effective treatment for rapid symptom resolution in this patient group.