Leptomeningeal cancer is a rare complication of cancer in which the disease spreads from the original tumor site to the meninges surrounding the brain and spinal cord. This leads to an inflammatory response, hence the alternative names neoplastic meningitis (NM), malignant meningitis, or carcinomatous meningitis. The term leptomeningeal (from the Greek lepto, meaning 'fine' or 'slight') describes the thin meninges, the arachnoid and the pia mater, between which the cerebrospinal fluid is located. The disorder was originally reported by Eberth in 1870. It is also known as leptomeningeal carcinomatosis, leptomeningeal disease (LMD), leptomeningeal metastasis, meningeal metastasis and meningeal carcinomatosis. It occurs with cancers that are most likely to spread to the central nervous system. The most common cancers that spread to the leptomeninges are breast cancer, lung cancer, and melanomas because they can metastasize to the subarachnoid space in the brain which offers a hospitable environment for the growth of metastatic tumor cells. Individuals whose cancer has spread to an area of the brain known as the posterior fossa have a greater risk of developing a leptomeningeal cancer. The condition can also arise from primary brain tumor like medulloblastoma. Leptomeningeal disease is becoming more evident because cancer patients are living longer and many chemotherapies cannot reach sufficient concentrations in the spinal fluid to kill the tumor cells.
Signs and symptoms Depending on where the tumor cells settle, leptomeningeal cancer can cause almost any neurological problem. The most common symptoms of leptomeningeal cancer are pain and seizures. The other symptoms may include headaches (usually associated with nausea, vomiting, light-headedness), gait difficulties from weakness or ataxia, memory problems, incontinence, and sensory abnormalities. In some cases, symptoms may include double vision, vision loss, numb chin, back pain, leg weakness, sphincter-related problems, hydrocephalus, loss of urine control, and difficulty walking. Other symptoms that are less common cranial nerve abnormalities, spinal symptoms such as limb weakness and paresthesia, and bowel and bladder dysfunction. Diplopia is the most common symptom of cranial nerve dysfunction. Trigeminal sensory or motor loss, cochlear dysfunction, and optic neuropathy are also common findings. Spinal signs and symptoms include weakness, dermatomal or segmental sensory loss, and pain in the neck, back, or following radicular patterns. 3 affected domains of neurological function:
Cerebral hemisphere (15%) Cranial nerves (35%) Spinal cord and roots (60%) Signs reported:
Headache Mental status change Confusion Cognitive impairment Seizures Hemiparesis Gait instability
Related diseases Parenchymal disease occurs in 30% to 40% of those diagnosed with NM. The disease associated with the main functioning body of an organ, in this case the brain. Acute cerebellar ataxia is a rare initial presenting feature of NM, particularly in gastric cancer. Paraneoplastic cerebellar degeneration (PCD) is a well-known cause of cerebellar ataxia associated with neoplastic disorders, and commonly, with positivity for various anti-neuronal antibodies. Bilateral sensorineural hearing loss caused by complications with the vestibulocochlear nerves from onset of NM Subacute confusion: when functioning of the brain such as cognition deteriorates but at a less rapid rate than that of acute confusion
Causes Leptomeningeal carcinomatosis occurs when the cancer cells invade the cerebrospinal fluid and spread throughout the central nervous system. The metastatic tumor cells grow either attached to the pia mater covering the brain and spinal cord or floating unattached to the subarachnoid space. Tumors of diverse origins and hematologic cancers may spread to this space. Some patients may develop leptomeningeal cancer while receiving chemotherapy for their primary tumour, partly because the blood-brain barrier serves as a protective filter that shields the central nervous system from toxins and pathogens circulating in the blood. While essential for protection, this barrier also complicates treatment, as many chemotherapy agents and biopharmaceuticals struggle to cross into the brain and spinal cord.
Pathology There are three anatomic patterns by which the tumor can spread in the subarachnoid space. More than one pattern may coexist in the same patient. First, there may be plaque-like deposits of cells in the leptomeninges with invasion of Virchow-Robin spaces and, usually, the shedding of tumor cells into the cerebrospinal fluid. Second, there may only be a thin coating of meninges, in some cases with only a single cell layer, but also with shedding of tumor cells into the cerebrospinal fluid. Third, there may be a pattern of nodular deposits of tumor on cranial and spinal nerve roots, frequently without tumor cells being shed into the cerebrospinal fluid. The first and third patterns are common in solid tumors whereas the second occurs most frequently with leukemia and lymphoma.
Spinal cord Neoplastic meningitis (NM) shows diffuse infiltration of tumor cells into the subarachnoid space which may be associated with increased intracranial pressure, signs of meningeal irritation, and damage to the cranial and spinal nerve roots. Pathological feature include:
Circular necrosis of the white matter in the periphery of the spinal cord was also noted which probably resulted from circulatory disturbance secondary to tumor infiltration. Dorsal radiculopathy which is secondary ascending degeneration of the posterior funiculus may also occur due to malignant cells collecting or a presence of tumor which cause compression of the nerve. Tumor cell proliferation is observed around nerve roots as well as loss of myelinated nerve fibers and axonal swelling. In areas of tumor cells, infiltration of macrophages is observed. Nerve root infiltration has shown positive correlation with meningeal dissemination. Infiltration of the spinal cord parenchyma is found with destruction of the pia mater. Tumor cell infiltration is associated with spongy changes in the white matter of the spinal cord beneath the pia mater with demyelination, axonal swelling, and macrophage infiltration. Transverse necrosis of the spinal cord is usually marked with bleeding from tumor growth in the subarachnoid space and is the result of compression by the hematoma in the subarachnoid space.
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