Leptomeningeal disease

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Leptomeningeal disease (LMD) is also commonly referred to as Carcinomatous meningitis or Neoplastic Meningitis. Typically LMD is a result of the spread of either primary or metastatic disease to the leptomeningeal space and is often diagnosed by imaging or cerebrospinal fluid cytology. These subarachnoid tumor cells are not as easily targeted by systemic chemotherapy and may proliferate. Thus, as systemic therapies improve, the incidence of LMD increases (as do brain metastases in general).
Axial T1 weighted MRI showing ventricular casting with tumor after resection of a left parietal GBM


Leptomeningeal disease (LMD) is the dissemination of cancer throughout the spinal fluid. Cancer cells may coat the leptomeninges (pia and arachnoid). LMD may often coat cranial nerves or the cauda equina. This may result in cranial nerve deficits or radiculopathy.


The exact incidence is difficult to ascertain since LMD is not often recognized. The overall incidence from few large series is estimatee to be between 0.8 to 8% of cancer patients, with the higher number being quoted in more recent publications. In solid tumors, the incidence ranges from 4-15%. Melanoma, lung and breast cancer are the most common sources of LMD in metastatic disease. It has also been frequently reported for primary tumors, especially Glioblastoma multiforme (GBM). May etiologies for LMD have been proposed including: hematogenous spread, spread via the perivascular lymphatic, endoneural or perineural routes, direct spread from CNS metastases, or iatrogenically after neurosurgical resection. Some studies suggested that en bloc resection of metastases will lower the LMD rate when compared to intralesional methods.

Clinical Presentation


Common symptoms include those associated with increased intracranial pressure. Headache, metnal status changes, nausea and vomiting, gait difficulty, seizures, and papilledema are frequent cerebral symptoms. Cranial nerve symptoms including visual loss, diplopia, hearing loss, dysphagia, ocular muscle weakness, facial weakness, and facial pain are also seen. For patients with spinal LMD, radicular pain, weakness, and paresthesias are also common.


The most useful diagnostic maneuver is lumbar puncture. Opening pressure is abnormal in >50% of patients, protein concentration is elevated in 80% of patients. Cytology is important, but this test is not very sensitive, and multiple lumbar punctures must be performed (at least 3) in order to make the diagnosis when clinical suspicion is high. At least 10cc of fluid should be evaluated. Ventricular fluid may also be evaluated but may be inconsistent with fluid obtained from lumbar puncture.


Sagittal T1 weighted MRI of patient with LMD from breast cancer. Note the linear enhancement on the spinal cord and deposit of enhancing material in the sacral thecal sac

T1 weighted MR with gadolinium is the standard imaging modality. Several imaging characteristics are seen in LMD including:

  • Intradural enhancing nodules
  • Enhancement of cranial nerves
  • Irregular tentorial enhancement
  • Irregular ependymal enhancement
  • Obliteration of the cisterns
  • Hydrocephalus
  • Subarachnoid or intraventricular enhancing nodules
  • Spinal linear enhancement
  • Assymetry of nerve roots


Cytologic evaluation is the gold standard. Malignant cells identified in the spinal fluid is diagnostic.


The mainstay of treatment is intrathecal chemotherapy. This is often performed with serial LPs for instillation of chemotherapy. More commonly, an Ommaya reservoir may be placed, sometimes in conjunction with a ventriculoperitoneal shunt if hydrocephalus is present. Focal irradation (or even whole brain radiation in patients who have not yet received it) may be offered. Chemotherapy may be delivered systemically or intrathecally. Systemic chemotherapy is limited by the blood brain barrier. The preferred treatment is delivery via Ommaya reservoir due to ease of access, certainty of delivery to the CSF, and better volume of distribution. Commonly used agents include:

  • methotrexate
  • DepoCyt (liposome encapsulated cytarabine)
  • Thiotepa

Systemic agents used include methotrexate and cytarabine.


The prognosis is probably more dependent upon the primary tumor histology, but LMD is an ominous development nonetheless. Impaired CSF dynamics, and bulk disease are poor predictors.


  1. Leptomeningeal metastases from solid malignancy: a review. Journal of Neuro-Oncology (2005) 75: 85–99
  2. Comparative risk of leptomeningeal disease after resection or stereotactic radiosurgery for solid tumor metastasis to the posterior fossa. J Neurosurg. 2008 Feb;108(2):248-57
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