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Leptomeningeal metastasis (LM) refers to the dissemination of malignant cells into the leptomeninges (pia mater and arachnoid mater) and the subarachnoid space, with spread via cerebrospinal fluid (CSF) pathways. It represents advanced systemic or CNS malignancy.

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Etiopathogenesis

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Tumor cells infiltrate subarachnoid space and CSF → coat cranial nerves, spinal roots, brain, and cord surfaces → obstruction of CSF flow → hydrocephalus and raised intracranial pressure.

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Sources of Spread

• Hematogenous dissemination → arterial seeding of leptomeninges.
• Direct extension from parenchymal brain metastases or skull/vertebral metastases.
• Iatrogenic: following surgery or intrathecal spread.

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• Detailed illustration: Anatomical routes of cancer cell entry into the leptomeninges </aside>

Common Primary Tumors

![Four main routes of cancer cells to enter CSF. 1: Via the arterial circulation by passing through the choroid plexus. 2: Via the venous circulation through Bateson’s plexus or bridging veins. 3: Via the cranial nerves or spinal roots perineurally. 4: Via penetrating the glia limitans from the brain parenchyma.

Figure adapted and created by F.F. Gellrich from Saadeh, F.; Boire, A. Leptomeningeal Disease and the Role of Intrathecal Therapy. In Central Nervous System Metastases: Diagnosis and Treatment; Ramakrishna, R., Magge, R.S., Baaj, A.A., Knisely, J.P.S., Eds.; Springer: Cham, Switzerland, 2020; pp. 169–186. ISBN 978-3-030-42958-4. Steininger J, Gellrich FF, Engellandt K, Meinhardt M, Westphal D, Beissert S, Meier F, Glitza Oliva IC. Leptomeningeal Metastases in Melanoma Patients: An Update on and Future Perspectives for Diagnosis and Treatment. International Journal of Molecular Sciences. 2023; 24(14):11443. https://doi.org/10.3390/ijms241411443](attachment:db5f0573-802d-47bc-b736-e701cc8ede2f:image.png)

Four main routes of cancer cells to enter CSF. 1: Via the arterial circulation by passing through the choroid plexus. 2: Via the venous circulation through Bateson’s plexus or bridging veins. 3: Via the cranial nerves or spinal roots perineurally. 4: Via penetrating the glia limitans from the brain parenchyma.

Figure adapted and created by F.F. Gellrich from Saadeh, F.; Boire, A. Leptomeningeal Disease and the Role of Intrathecal Therapy. In Central Nervous System Metastases: Diagnosis and Treatment; Ramakrishna, R., Magge, R.S., Baaj, A.A., Knisely, J.P.S., Eds.; Springer: Cham, Switzerland, 2020; pp. 169–186. ISBN 978-3-030-42958-4. Steininger J, Gellrich FF, Engellandt K, Meinhardt M, Westphal D, Beissert S, Meier F, Glitza Oliva IC. Leptomeningeal Metastases in Melanoma Patients: An Update on and Future Perspectives for Diagnosis and Treatment. International Journal of Molecular Sciences. 2023; 24(14):11443. https://doi.org/10.3390/ijms241411443

Clinical Features

Diffuse, multifocal neurological signs due to widespread CSF dissemination:

• Cerebral: headache, nausea, vomiting, seizures, cognitive dysfunction.
• Cranial nerves: diplopia (CN VI), facial weakness (CN VII), hearing loss (CN VIII).
• Spinal cord / roots: radiculopathy, limb weakness, paresthesias, cauda equina syndrome.
• Raised ICP: due to hydrocephalus (papilledema, altered sensorium).

Radiology