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Metastatic Disease

Metastases spread to the nervous system through the bloodstream (cerebral, spinal, and leptomeningeal metastases), lymphatic vessels (metastases to the PNS), and cerebrospinal fluid (so-called drop metastases in the spinal sub-arachnoid space). Aside from direct metastatic involvement, the nervous system can also be affected by local tumor infiltration (e.g., of the brachial plexus by a Pancoast tumor), by external compression (e. g., of the spinal cord by a vertebral tumor, or of a peripheral nerve by a tumor-infiltrated lymph node), or by perineural infiltration (e. g. melanoma or salivary gland carcinoma). Only a small fraction of proliferating tumor cells are capable of metastasizing; thus, the biological behavior and drug response of metastasizing cells may differ from that of the primary tumor. Angiogenesis is essential for tumor growth and metastasis. Local invasion of surrounding tissue by the primary tumor makes it possible for tumor cells to break off and metastasize by way of the lymphatic vessels, veins, and arteries. Metastatic cells often settle in a vascular bed just downstream from the site of the primary tumor, thus (depending on its location) in the lungs, liver, or vertebral bodies. The nervous system may become involved thereafter in a second phase of metastasis (cascade hypothesis), or else directly, in which case the metastasizing cells must have passed through the intervening capillary bed without settling in it. Metastases may also bypass the lungs through a patent foramen ovale (paradoxical embolism).

■ Intracranial Metastases

Of all intracranial metastases, 85% are supraten-torial, 15 % infratentorial. The primary process in men is usually a tumor of the lung, gastrointestinal tract, or urogenital system, in women a tumor of the breast, lung, or gastrointestinal tract. Prostate, uterine, and gastrointestinal tumors metastasize preferentially to the cerebellum. The clinical manifestations of in-tracranial metastases are usually due to their local mass effect and surrounding cerebral edema. Brain metastases of melanoma, chorio-carcinoma, and testicular cancer tend to produce hemorrhages. Metastases to the calvaria are usually asymptomatic. Skull base metastases cause pain and cranial nerve deficits. Dural-based metastases may compress or infiltrate the adjacent brain tissue, or exude fluid containing malignant cells into the subdural space. Pituitary metastases (mainly of breast cancer) cause endocrine dysfunction and cranial nerve deficits.

■ Spinal Metastases

The clinical manifestations of vertebral metastases, including vertebral or radicular pain, paraparesis/paraplegia, and gait ataxia, are mainly due to epidural mass effect. The bone marrow itself being insensitive to pain, pain arises only when the tumor compresses the periosteum, paravertebral soft tissue, nerve roots, or spinal cord. Spinal instability and pathological fractures cause additional pain. Pain in the spine may be the first sign of spinal metastasis. Subarachnoid and intramedullary metastases are rare (< 5%).

■ Leptomeningeal Metastases (Neoplastic Meningeosis, "Carcinomatous Meningitis")

Seeding of the meninges may be diffuse or mul-tifocal. Meningeal metastases may spread into the adjacent brain or spinal cord tissue, cranial nerves, or spinal nerves. Cerebral leptomening-eal involvement produces headache, gait ataxia, memory impairment, epileptic seizures, and cranial nerve deficits (e. g., facial nerve palsy, hearing loss, vertigo, diplopia, and loss of vision). Spinal involvement produces neck or back pain, radicular pain, paresthesia, paraparesis, and atony of the bowel and bladder.

Meningeal Metastases Photo

Patent foramen ovale Pulmonary metastases

Pathogenesis of cerebral metastasis

Patent foramen ovale Pulmonary metastases

Pathogenesis of cerebral metastasis

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