MRI of the lumbar spine (Fig. 19.2) shows multiple metastases along the cauda equina.

• Neurogenic: increased cerebrospinal fluid (CSF) pressure, intracranial hypotension
  
• Inflammatory: sarcoidosis
  
• Infectious: subacute and chronic meningitis including tuberculosis, fungal infection, granulomatous cell infiltration
  
• Vascular: local ischemia, venous thrombosis, hypoxia, subarachnoid hemorrhage
  
• Traumatic
  
• Drug induced: chemotherapeutic agents, heavy metals
  
• Neoplastic: local tumor infiltration, primary meningeal glioma, primitive neuroectodermal tumor, isolated primary meningeal melanomas, rhabdomyosarcoma of the leptomeninges1,2
  
• Other: ionizing radiation, metabolic disturbances, reaction to hyperventilation

• MC is estimated to occur in ~5% of all patients with cancer. There is a greater prevalence of solid tumors compared with hematologic malignancies³
  
• Hematologic malignancies presenting mostly with spinal or radicular symptoms
  
  
  
  • Breast and lung cancers
    
  • Head and neck cancers
    
  • Melanoma
    
  • Gastric cancer
  
  
• Hematologic malignancy presenting more frequently with cranial nerve dysfunction or multifocal neurologic symptoms
  
  
  
  • Leukemia
    
  • Lymphoma
    
  • Adenocarcinoma of unknown primary

• CSF cytology
  
• Radiologic studies
  
  
  
  • Cranial CT
    
  • Brain and spine MRI
    
  • CT myelography (rarely used)
  
  
• Radionuclide CSF flow studies
  
• Meningeal biopsy from an enhancing region on MRI, in cases where CSF exams remain inconclusive

• The initial cytology is falsely negative in up to 40–50% of patients with pathologically proven leptomeningeal carcinomatosis. Diagnostic yield improves with²
  
  
  
  • Repeated sampling (50% for the first to 90% for the third spinal tap)
    
  • CSF sample volume (10 mL at least)
    
  • Avoiding delays in (i.e., immediate) processing and cytospin of the samples in the laboratory
    
  • Sampling site (LP provides a higher yield than ventricular CSF)

• Hematogenous spread via the arterial circulation or retrograde venous pathways along the valveless Batson venous plexus
  
• Perineural and perivascular lymphatics route
  
• Direct spread from central nervous system (CNS) tumors into the subarachnoid or ventricular spaces
  
• Iatrogenic spread during invasive procedures or neurosurgery through an ependymal or dural breach
  
• Common pathway: Once malignant cells enter the CSF, they disseminate to distant parts of the CNS, where they form secondary leptomeningeal deposits. The areas of predilection are basilar cisterns, posterior fossa, and cauda equina.²

• Enhancement and enlargement of cranial nerves
  
• Superficial linear sulcal, cisternal, or dural enhancement
  
• Irregular tentorial or ependymal enhancement
  
• Cisternal or sulcal obliteration
  
• Communicating hydrocephalus
  
• Subarachnoid or intraventricular enhancing nodules
  
• Multiple small nodular superficial brain nodules
  
• Spinal linear enhancement
  
• Spinal cord enlargement
  
• Asymmetry of the roots with clumping of the roots of the cauda equina^1,2

• Symptomatic treatment includes
  
  
  
  • Pain relief using analgesics: acetaminophen, opioids
    
  • Neuropathic pain often requires amitriptyline, clonazepam, or antiepileptic drugs (AEDs) such as egabalin (Lyrica; Pfizer Pharmaceuticals, New York, NY) or gabapentin (Neurontin; Pfizer Pharmaceuticals, New York, NY).
    
  • Focal irradiation of symptomatic sites is often quite efficient in relieving pain.
  
  
• Seizures are managed with anti-epileptic drugs (AEDS), but prophylactic administration of AEDs is not recommended in patients who have never had seizures.
  
• Headaches related to edema or increased intracranial pressure can sometimes be treated with steroids.
  
• In cases of hydrocephalus secondary to CSF blockade, a course of steroids during whole brain or skull-base radiotherapy (RT) is sometimes appropriate, but shunting is often required.
  
• Repeated LPs in the absence of cerebral edema or mass effect are often a good way to relieve headache.

• Advantages over repeated LP4:
  
  
  
  • Drug administration is painless and easier to perform.
    
  • Better drug distribution in the entire subarachnoid ventricular spaces
    
  • Possibility of delivering frequent small doses of drug to reduce neurotoxicity
    
  • Can be used when the platelet count is around 20,000 cell/mm³
    
  • Provides a certainty that the drug has not been given in the epidural space (which is the case in 10% of LPs)
    
  • Avoids some complications of LPs such as
    
    
    
    • Local obstruction of CSF circulation secondary to arachnoiditis
      
    • Brain herniation in the presence of brain mass effect
  
  
• Complications⁵
  
  
  
  • If there is a concern due to risks for general anesthesia, it can be performed with local anesthesia.
    
  • Infections
    
  • Epilepsy by extravasation of the drug into the brain
    
  • Failure to puncture slit ventricles
    
  • Hemorrhages are rare complications occurring especially with repeated puncture attempts.
    
  • Reservoir or catheter obstruction or dysfunction

• The treatment of meningeal carcinomatosis today is palliative and rarely curative with a median patient survival of 2 months. However, palliative therapy often aff ords the patient protection from further neurologic deterioration and consequently an improved neurologic quality of life.³
  
• Radiotherapy
  
  
  
  • Although it may stabilize or delay progression of neurologic symptoms, it does not prolong survival.³
    
  • RT is also indicated to relieve CSF blocks, which reduce the efficacy and increase the toxicity of intrathecal chemotherapy.
    
  • RT is administered at a dose of 30 Gy delivered in 10 fractions over 2 weeks. It provides effective relief of pain and stabilizes neurologic symptoms but rarely leads to significant recovery²
    
  • Irradiation of the entire neuraxis is too toxic in patients who have generally already received multiagent chemotherapy and are prone to severe bone marrow toxicity.
  
  
• Chemotherapy
  
  
  
  • Chemotherapy can be administered intrathecally and/or systemically. Methotrexate is usually the first-line agent followed by cytarabine and thiotepa.
    
  • Following the placement of an intraventricular catheter, methotrexate may be administered as 2 mg per day for 5 consecutive days every other week for four treatment cycles^2–4
  
  
• Prophylactic treatment in lymphoma and leukemia
  
  
  
  • Prevention of CNS relapse is increasingly a goal of primary therapy for patients with either non-Hodgkinߛs lymphoma or acute lymphocytic leukemia, high-dose systemic and/or intrathecal chemotherapy are used depending on the presence of risk factors for CNS involvement. These risk factors include
    
  • Lymphoma grade and stage
    
    
    
    • Extent of extranodal disease
      
    • Young age
      
    • Elevated serum lactate dehydrogenase levels
      
    • Presence of human immunodeficiency virus-(HIV)-related NHL
      
    • Presence of a primary CNS lymphoma³

• Despite therapy, median survival for meningeal carcinomatosis is about 4 months from diagnosis. This is particularly true of patients with leptomeningeal metastasis from solid tumors. Patients with breast cancer have a relatively better prognosis with median survival of 6 months from the time of diagnosis of meningeal carcinomatosis.
  
• Patients with leukemia and lymphoma have the best prognosis with meningeal carcinomatosis. Such patients may respond rapidly and remain in a sustained remission for months to years.⁴