From the Guidelines
A white blood cell (WBC) count of 13 cells/μL in cerebrospinal fluid (CSF) with leptomeningeal involvement suggests an inflammatory or infectious process affecting the meninges, and the patient should undergo immediate diagnostic evaluation and treatment, prioritizing empiric antimicrobial therapy and further diagnostic tests such as CSF glucose, protein, Gram stain, culture, viral PCR, and fungal studies, as well as brain imaging with contrast-enhanced MRI to evaluate the extent of leptomeningeal involvement, as recommended by recent guidelines 1.
Key Considerations
- The elevated WBC count in CSF, although mild, combined with leptomeningeal findings, indicates an active pathological process requiring urgent attention to prevent neurological complications.
- Empiric antimicrobial therapy should be initiated promptly, covering common pathogens, including Listeria in patients over 50 years, and considering viral meningitis if suspected, with the addition of acyclovir 1.
- Diagnostic tests should include CSF analysis for glucose, protein, and cytology, as well as imaging studies like MRI to assess the extent of leptomeningeal involvement and guide further management.
- If malignancy is suspected as the cause of leptomeningeal disease, consultation with oncology for potential intrathecal chemotherapy should be considered, given the poor prognosis associated with leptomeningeal metastases from solid tumors 1.
Management Approach
- The management of leptomeningeal metastases involves a multidisciplinary approach, including palliative care, radiation therapy, systemic therapy, and intrathecal therapy, with the goal of improving survival and quality of life 1.
- Systemic therapies with CNS bioactivity should be prioritized, and investigations of these therapies should include CSF pharmacokinetic and pharmacodynamic analyses to better understand blood-CSF barrier permeability and local bioactivity.
- Intrathecal chemotherapies are most effective in patients with thin linear leptomeningeal deposits and unobstructed CSF flow, and the development of new intrathecal therapies would benefit from standardization of preclinical testing and drug preparation.
From the Research
Leptomeningeal Disease Diagnosis
- The diagnosis of leptomeningeal disease can be challenging, and cerebrospinal fluid (CSF) examination is helpful in detecting the disease, especially when MRI is negative 2.
- CSF cytological investigation is mandatory whenever leptomeningeal metastasis is suspected, even when CSF cell count is normal 2.
- Flow cytometry can increase the sensitivity and specificity of leptomeningeal disease detection in CNS lymphomas, and it should be applied concurrently with cytopathology for complementary diagnostic assessment 3.
CSF Parameters and Leptomeningeal Metastasis
- Elevated CSF lactate levels and blood-CSF-barrier dysfunction are common in patients with leptomeningeal metastasis, but significant correlations between these parameters and MRI findings are not always found 2.
- Oligoclonal bands in CSF can be present in a high number of patients with leptomeningeal metastasis, but their significance is not fully understood 2.
- A high white blood cell (WBC) count in CSF, such as WBC 13, can be indicative of leptomeningeal disease, but further investigation, including CSF cytology and flow cytometry, is necessary to confirm the diagnosis 2, 3, 4.
Diagnostic Strategies
- Diagnosis of leptomeningeal disease is definitively made via CSF cytology for malignant cells, but neuro-imaging with high-quality T1-weighted magnetic resonance imaging can aid diagnosis and localization 5.
- Flow cytometry immunophenotyping can contribute to detecting leptomeningeal disease in patients with solid tumors, with higher sensitivity and negative predictive value compared to CSF cytology 6.
- A combination of technical procedures, including CSF cytology, flow cytometry, and fluorescence in situ hybridization, can help identify patients with leptomeningeal myelomatosis, a rare but devastating manifestation of multiple myeloma 4.