BSLD-05 LEPTOMENINGEAL DISEASE IN THE MODERN ERA: THE HOLISTIC REVIEW OF RISK FACTORS, PATHOLOGY, AND TREATMENT SEQUALE

Abstract

Leptomeningeal disease (LMD) involves pathology of the pia mater, arachnoid mater, and subarachnoid space. The most common form is leptomeningeal carcinomatosis, which may arise from primary CNS tumors or, more commonly, as secondary metastasis from systemic malignancies such as breast cancer, lung cancer, melanoma, and hematological cancers. Other causes include infections, autoimmune disorders, and tumor-like conditions, making diagnosis challenging due to overlapping clinical and imaging features. Risk factors include advanced or metastatic cancer, high tumor burden, prior CNS involvement, aggressive tumor biology, and inadequate therapeutic penetration into cerebrospinal fluid (CSF), allowing malignant cells to persist and proliferate. Despite protective barriers like the blood-brain and blood-CSF barriers, malignant cells spread via hematogenous dissemination, direct invasion, or CSF seeding. Molecular mediators such as VEGF and chemokine pathways (e.g., CXCR4/SDF-1) facilitate tumor migration, angiogenesis, and CNS infiltration. Clinically, LMD presents with nonspecific but progressive neurological symptoms, including headache, nausea, vomiting, cranial nerve deficits (visual or auditory disturbances), seizures, limb weakness, back pain, gait abnormalities, and altered mental status, reflecting multifocal CNS involvement. Diagnosis relies on CSF analysis and neuroimaging. CSF cytology remains the gold standard, often showing malignant cells, elevated protein, reduced glucose, and increased opening pressure. Gadolinium-enhanced MRI is the imaging modality of choice, typically demonstrating pial enhancement, nodularity, and nerve root involvement. CSF flow studies can further identify obstructive patterns. Management includes focal radiotherapy for symptomatic relief, followed by intrathecal chemotherapy (e.g., methotrexate, cytarabine, trastuzumab) and systemic therapies such as pemetrexed, bevacizumab, and targeted agents. Surgical interventions like ventriculoperitoneal shunting or intraventricular catheter placement may be required in selected cases.Treatment-related adverse effects include neurological symptoms, fatigue, cognitive decline, immunosuppression, and catheter-related complications. Therefore, multidisciplinary care is essential to optimize outcomes and preserve quality of life.