Makindo Medical Notes

About

• Leptomeningeal metastases (LM) occur when malignant cells spread to the pia and arachnoid mater, seeding within the cerebrospinal fluid (CSF) pathways.
• Also called carcinomatous meningitis or neoplastic meningitis.
• Represents a late and serious complication of systemic malignancy, seen in up to 5–8% of solid tumours and many haematological cancers.
• Common primaries: breast (especially HER2⁺), lung (adenocarcinoma), and melanoma. Haematological sources include lymphoma and leukaemia.

Pathophysiology 🧩

• Malignant cells reach the meninges via:
  • Haematogenous spread through choroid plexus or venous plexus.
  • Direct extension from parenchymal or bone metastases.
  • Perineural or perivascular invasion.
• Once in CSF, tumour cells circulate and adhere to the leptomeninges, forming nodular deposits that disrupt CSF flow and absorption.
• This leads to raised intracranial pressure (ICP), cranial nerve palsies, and radiculopathies.
• Inflammatory cytokines and disrupted blood–CSF barrier contribute to oedema and neurological dysfunction.

Clinical Features ⚠️

• Symptoms are often multifocal and fluctuate over time.
• Headache, nausea, vomiting → due to raised ICP.
• Cranial nerve deficits — diplopia, facial weakness, hearing loss (most often VI, VII, VIII involvement).
• Radicular pain or limb weakness from spinal root infiltration.
• Cognitive decline or encephalopathy in advanced cases.
• Seizures can occur due to cortical irritation.

Investigations 🔍

• MRI with contrast is the imaging of choice — shows linear or nodular leptomeningeal enhancement over brain, cerebellum, or cord.
• CSF cytology is diagnostic if malignant cells are seen (yield ~50% on first tap, up to 80–90% with repeat sampling).
• CSF: raised protein, low glucose, mild lymphocytosis; sometimes xanthochromia.
• Consider tumour markers (CEA, CA15-3, PSA) in CSF if diagnosis uncertain.
• Always exclude infection (e.g. TB, fungal meningitis) in immunocompromised patients.

Management 🩺

• Goals: relieve symptoms, maintain neurological function, and prolong quality life.
• Corticosteroids (e.g. dexamethasone 4–8 mg twice daily) can improve headache and cranial nerve symptoms by reducing oedema.
• Systemic therapy: modern targeted and immune therapies (e.g. trastuzumab, osimertinib, pembrolizumab) increasingly achieve CSF penetration and disease control in specific cancers.
• Intrathecal chemotherapy (methotrexate, cytarabine, thiotepa) may be used when disease is CSF-predominant and systemic therapy insufficient.
• Focal radiotherapy can palliate bulky deposits or symptomatic nerve root compression.
• Supportive care: anticonvulsants, analgesia, management of raised ICP, and involvement of palliative care early.

Prognosis 📉

• Historically poor: median survival 4–8 weeks untreated, but improving with targeted therapies.
• Selected patients on modern systemic or intrathecal therapy can achieve 6–12 months or longer survival.
• Prognosis best with: controlled systemic disease, preserved performance status, and targetable tumour mutations.

Teaching Point 🧠

Leptomeningeal metastases are a hallmark of advanced, disseminated cancer. Early recognition matters — subtle cranial neuropathies or new radicular pain in a known malignancy warrant MRI and CSF evaluation. Management focuses on symptom control, maintaining neurological function, and, when possible, leveraging targeted or intrathecal therapies for disease modulation.

UK Context 🇬🇧

• Diagnosis and management are usually led by neuro-oncology MDTs in tertiary centres.
• NICE supports the use of targeted systemic therapy in leptomeningeal involvement when molecularly indicated (e.g. EGFR-mutant, HER2⁺).
• Palliative care integration is essential — early involvement improves quality of life and reduces hospital admissions.

References 🔗

• Chamberlain MC, Soffietti R et al. ESMO Clinical Practice Guidelines for Brain and Leptomeningeal Metastases. Ann Oncol 2023.
• Le Rhun E et al. Lancet Neurol 2019;18:1112–1124.
• NCCN Guidelines: CNS Cancers v2.2024.
• UK NICE. Cancer service guidance: Improving outcomes for people with brain and CNS tumours.