Metastasis to the brain can be in the brain parenchyma or the meninges covering it. The later is known as leptomeningeal metastasis and can be from extraneural or intraneural primary site . It is also known as neoplastic meningitis and is mostly a late-stage complication of systemic cancers. Overall incidence is 4–15% .
Systemic cancer most commonly involving LM are breast cancer (BC) followed by non-small cell lung cancer (NSCLC) and melanoma. The incidence of LM in BC, NSCLC and melanoma is 5%, 11% and 20%, respectively [5,6,7,8,9]. Central nervous system (CNS) involvement is seen clinically in 30% of patients with melanoma and as high as 75% at autopsy . The increased incidence of LM is due to more effective diagnostic modalities, adjuvant and salvage systemic therapies and non-effective chemotherapy to these metastatic cells due to the blood brain barrier leading to a prolongation of survival and late metastatic spread to the CNS .
Tumor cells pathway to the meninges can be different in which the most common form of spread is hematogenous followed by lymphatic, direct, choroid, de novo and iatrogenic . The most affected areas are basilar cisterns and cauda equina .
LM manifests as a multifocal constellation of neurologic signs and symptoms. Common symptoms include cranial nerve deficits, radicular pain, headache, back pain, visual disturbances, diplopia, hearing loss, onset of psychiatric disorders, seizures and cauda equina syndrome . Headache and confusion were common cerebral symptoms at presentation, with headache occurring in 39% of patients . A high index of suspicion needs to be entertained to make the diagnosis of LM. Due to non-specific and pleomorphic presentations, other diagnoses are entertained like primary brain cancer, chronic meningitis, paraneoplastic syndromes and subdural hematoma.
Amongst the diagnostic modalities, magnetic resonance imaging (MRI) with gadolinium enhancement is the radiologic technique of choice. The most frequent MRI findings are subarachnoid and parenchymal enhancing nodules and diffuse or focal pial enhancement. The sensitivity of MRI varies from 20 to 91%. CT is of limited value in the diagnosis of LM. The sensitivity of CT scan is estimated at 23‑38%, and it mostly shows hypodense lesions . One must be able to differentiate chronic subdural hematoma from LM which can be our first diagnosis when the primary lesion is not known and patient presents with non-specific symptoms and a hypodense lesion with mass effect.
Leptomeningeal disease is difficult to treat, with generally poor outcomes. Primary treatment goals include improvement of the patients neurological deficits and quality of life, while avoiding toxicity. Pain relief is required for headaches, back and radicular pain and is based on the use of analgesics of increasing efficacy from acetaminophen to opioids. Seizures are treated with antiepileptic drugs. Surgery in LM is used for management of raised intracranial pressure requiring ventriculoperitoneal shunting (VPS) . Intra cerebrospinal fluid (CSF) Methotrexate, Ara-C, cytarabine, Thiotepa can be used but showed less effectiveness .
Systemic treatments also showed modest response in BC, NSCLC and melanoma related LM . In melanoma, intensive schedule of combinatorial temozolomide, ipilimumab, vermurafenib, dabrafenib or trametinib can be used . Surgical excision of LM is not a treatment modality.
Without treatment, the median overall survival of patients with LM is approximately 6 weeks . Despite advances, survival remains poor after diagnosis of leptomeningeal involvement, averaging around 3–6 months . Melanoma related LM has the worst prognosis of all solid tumor related LM with median survivals between 10 weeks and 4 months [13,14,15].
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.