Leptomeningeal disease (LMD) is a serious complication where cancer cells spread to the thin layers of tissue (leptomeninges: arachnoid and pia mater) covering the brain and spinal cord, and enter the cerebrospinal fluid (CSF).
It is also known as leptomeningeal metastasis, leptomeningeal carcinomatosis, or neoplastic meningitis.
Its most common primary cancers: Breast cancer, lung cancer, melanoma, leukemia, and lymphoma have the highest risk of spreading to the leptomeninges.
An estimated 5 to 10% of patients with metastatic carcinoma will develop LMD particularly from breast, lung, melanoma, or G.I. cancers.
Tumor cell dissemination through the CNS results in the diverse presentation of neurologic symptoms that can be both debilitating and life-threatening.
Symptoms of LMD are often related to nerve injury or increased intracranial pressure due to CSF obstruction or resorption, including intractable headaches, cranial neuropathies, progressive, weakness, bowel, and bladder dysfunction, and seizure.
The incidence of LMD is increasing.
Leptomeningeal metastases results in substantial morbidity and mortality.
The median survival of patients is often measured in weeks to months with standard treatment.
Symptoms: Can include headaches, nausea, vomiting, confusion, weakness, visual disturbances, seizures, sensory or motor problems, back/neck pain, changes in urination or bowel function, and cranial nerve deficits.
Diagnosis involving neurological examination, MRI scans and CSF analysis to detect malignant cells.
Treatment: Usually combines surgery, radiation, and chemotherapy, sometimes delivered directly into the CSF via an Ommaya reservoir or by lumbar puncture.
Treatment approaches are usually palliative as intrathecal chemotherapy, photo based cranial spinal radiation are associated with substantial toxic effects without meaningful survival benefit to date.
LMD can progress rapidly, leading to significant neurological impairment.
The overall prognosis is generally poor.
Leptomeningeal disease is increasingly recognized as cancer patients live longer.
Leptomeningeal disease is the pathological infiltration of malignant cells into the leptomeninges, which are the pia mater and arachnoid mater, and the subarachnoid space surrounding the brain and spinal cord.
This process commonly occurs as a late-stage complication of systemic cancers, including solid tumors, such as breast cancer, lung cancer, and melanoma, and hematologic malignancies, such as lymphoma and leukemia).
The presence of malignant cells in the leptomeningeal compartment leads to multifocal neurological symptoms due to widespread involvement of the central nervous system: cranial neuropathies, radiculopathies, encephalopathy, and signs of increased intracranial pressure.
Diagnosis is established by detecting malignant cells in the cerebrospinal fluid (CSF) by cytology, often supported by neuroimaging (MRI with gadolinium), although both modalities have limitations in sensitivity and specificity.
Leptomeningeal disease is associated with a poor prognosis, with median survival typically measured in weeks to a few months.
Treatment is palliative and may include intrathecal or systemic chemotherapy, radiation therapy, and supportive care, but outcomes remain poor.
Because leptomenial metastases disseminate throughout the entire CNS compartment in field radiation therapy cannot halt the progression aggression along the entire neuraxis.
In field radiation therapy has not been demonstrated to consistently improve survival.
Proton therapy deposits the bulk of the energy at the last few millimeters of its range and proton cranial spinal irradiation results in minimal RT dose beyond the neuraxis and is associated with significantly fewer toxic effects compared with photon based craniospinal radiation 9Yang JT).
Improved CNS progressive free survival and overall survival has been noted with proton craniospinal radiation compared with in field radiation.