Neoplastic meningitis (patient information)

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Neoplastic meningitis
Overview
What are the symptoms?
What are the causes?
Who is at highest risk?
Diagnosis
When to seek urgent medical care?
Treatment options
Where to find medical care for Neoplastic meningitis?
Prevention
What to expect (Outlook/Prognosis)?
Possible complications
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Overview

• Neoplastic meningitis is a secondary cancer of the subarachnoid space, meninges and pia matter from a primary tumor source. It is one of the dreaded complications of terminal malignancy. It could be from a distant metastasis or from a primary brain tumor. Most commonly documented primary distant source is beast cancer.

What are the symptoms of Neoplastic meningitis?

• The 3 affected neurologic domains of neoplastic meningitis in order of involvement is spinal cord and roots (60%) cranial nerve (35%) and cerebral hemisphere (15%)[1]
  • Documented spinal cord manifestations of NM include: weakness (upper limb greater than the lower limb), sensory deficits in dermatomal origin and pain in the neck, back and upper extremity that is most frequently radicular.
  • Cranial nerve manifestation includes diplopia which is the most common sign in this category; trigeminal sensory and motor loss, cochlear dysfunction and optic neuropathy have also been observed.
  • Cerebral hemisphere manifestations are mostly vague and non-specific includes headache and mental status changes.
• Symptoms are often multifocal and neuraxal. The most common presenting symptom of neoplastic meningitis is pain or seizure. [2]

What causes Neoplastic meningitis?

• Neoplastic meningitis is caused by another tumor seeding into the CNS
  • Cancer from a distant source enter the CSF by means of the following:[3]
    • Hematogenous Spreadfrom a distant primary tumor site - cancer cells produce enzymes that allows them to microscopically invade blood vessels to reach the subarachnoid space through the systemic arterial circulation or by the Batsons venous plexus.
    • Invasion from a primary brain tumor to the meninges - when cancer cells lodge into small arteries causing local ischemia and blood vessel damage leading to spillage of neoplastic cells to the Virchow-Robin spacesthereby providing access to the subarachnoid space.
    • Infiltration to the spinal cord - Cancer cells gain access to the subarachnoid space through this route via the perivascular tissues the surround the blood vessels at the brain entrance. Direct infiltration of the spinal nerve roots (dorsal and ventral) has also been documented.
    • Cancer spread a neural pathways to reach the meninges - The CSF carries cancer cells through the brain tracts. This occurs mostly in tumors of the head and neck.[4]
    • Iatrogenic - from surgical procedures involving removal of a primary brain tumor
  • Primary neoplastic meningitis has also been documented particularly with melanoma.[5]
    

Who is at highest risk?

• Patients with advanced breast cancer have increased propensity for NM. ER-, PR-positivity in beast cancer increases incidence of neoplastic meningitis. Triple negative breast cancer and the HER2/neu gene positivity displays tropism for CNS metastasis. Among the histologic subtypes of breast cancer, loblular carcinoma demonstrated the highest prevalence for neoplastic meningitis.
• Brain surgery increases the chance of developing NM. It has been observed after resection of brain tumor (particularly piecemeal resection vs en-block resection) particularly tumors located in the cerebellum. Other cranial surgeries done with involvement of ventricular system manipulation in a patient with known brain metastasis increases the risk. Furthermore, the incidence of neoplastic meningitis seem higher in patient treated with surgery followed by stereotactic radiosurgery compared with radiosurgery alone.
• Primary brain cancer always poses a risk for the development of neoplastic meningitis. It is diagnosed in 1-2% of cases of ependymoma, medulloblastoma, germinoma and glioblastoma combined.
• Brain metastasis is one of the more obvious risk factors for neoplastic meningitis. Coexisting brain metastasis are associated with neoplastic meningitis in breast cancer (33-54%), lung cancer (56-82%) and melanoma (87-96%).

Diagnosis

• This is a proposed algorithm for the diagnosis of NM [6]

When to seek urgent medical care?

• Patients with documented cancer manifesting with signs and symptoms of increased intracranial pressure, cardiorespiratory distress and sudden onset neurological deficiets should seek urgent care.

Treatment options

• Treatment is palliative and is aimed at preventing and reducing neurological deficits and extending survival with good quality of life. Treatment is composed of any or all of the three components: radiotherapy, intraventricular or intrathecal chemotherapy and systemic radiotherapy. [7]

Where to find medical care for Neoplastic meningitis?

Directions to Hospitals Treating Neoplastic meningitis

Prevention of Neoplastic meningitis

• There is no documented prevention measures for the development of NM.

What to expect (Outlook/Prognosis)?

• The rates of survival for neoplastic meningitis varies depending on the source of primary tumor, but generally median survival rate without treatment is limited to 1 to 2 months. With treatment, this could extend to 2 to 5 months for breast cancer, 3 to 6 months for non-small cell lung cancer and 2 to 4 months for melanoma. Factors affecting the prognosis of patients with neoplastic meningitis includes gene involvement and use of immunotherapy and other targeted therapies. For breast cancer, ER-positivity, lesser extend of initial disease and better performance status has been demonstrated to have better prognosis. For lung cancer, the use of epidermal growth factor (EGFR) inhibitors confers durable responses without the need for intra-CSF chemotherapy administration. Lastly, for melanoma, primary tumors located in the trunk has been documented to have a poor prognosis, but intra-CSF administration of chemotherapy significantly improves this prognosis.
• Not surprisingly, patients with poor performance status, multiple fixed neurological deficits, bulks CNS disease, co-existent carcinomatous encephalopathy and CSF flow abnormalities will do poorly with intensive treatment of disease. Death typically results from progression of neurological dysfunction.
• Some retrospective studies have demonstrated favorable outcomes in neoplastic meningitis: age less than 60, long duration of symptoms, controlled systemic disease, Karnofsky performance status >/= 70, absence of encephalopathy or cranial nerve deficit, initially low CSF protein level, absence of CSF compartamentalization or bulky CNS disease manifested by impedance of CSF flow and history of primary breast tumor.