Leptomeningeal cancer (also called leptomeningeal carcinomatosis, leptomeningeal disease (LMD), leptomeningeal metastasis, neoplastic meningitis, meningeal metastasis and meningeal carcinomatosis) 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 Pia mater ( or ),Entry "pia mater"
in
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

is located. The disorder was originally reported by Eberth in 1870. It occurs with cancers that are most likely to spread to the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

. The most common cancers to include the

leptomeninges In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in th ...

are

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...

, 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 Medulloblastoma is a common type of primary brain cancer in children. It originates in the part of the brain that is towards the back and the bottom, on the floor of the skull, in the cerebellum, or posterior fossa. The brain is divided into two ...

. 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

The most common symptoms of leptomeningeal cancer is 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, sensory abnormalities. In some cases, symptoms may include double vision, numb chin, back pain, leg weakness, sphincter-related problems, hydrocephalus, loss of urine control, and difficulty walking. Depending on where the tumor cells settle, leptomeningeal cancer can cause almost any neurological problem. Other symptoms that are less common cranial nerve abnormalities, spinal symptoms such as limb weakness and paresthesia, and bowel and bladder dysfunction.

Diplopia Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often v ...

is the most common symptom of cranial nerve dysfunction.

Trigeminal In neuroanatomy, the trigeminal nerve ( lit. ''triplet'' nerve), also known as the fifth cranial nerve, cranial nerve V, or simply CN V, is a cranial nerve responsible for sensation in the face and motor functions such as biting and chewing; ...

sensory or motor loss,

cochlea The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory or ...

r 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 Radicular pain, or radiculitis, is pain "radiated" along the dermatome (sensory distribution) of a nerve due to inflammation or other irritation of the nerve root (radiculopathy) at its connection to the spinal column. A common form of radicul ...

patterns. 3 affected domains of neurological function: *

Cerebral hemisphere The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres ...

(15%) *

Cranial Nerves Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...

(35%) * Spinal cord and roots (60%) Signs reported: * headache * mental status change * confusion * cognitive impairment * seizures *

hemiparesis Hemiparesis, or unilateral paresis, is weakness of one entire side of the body ('' hemi-'' means "half"). Hemiplegia is, in its most severe form, complete paralysis of half of the body. Hemiparesis and hemiplegia can be caused by different medi ...

* gait instability

Related Diseases

* Parenchymal Disease occurs in 30-40% 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 The vestibulocochlear nerve or auditory vestibular nerve, also known as the eighth cranial nerve, cranial nerve VIII, or simply CN VIII, is a cranial nerve that transmits sound and equilibrium (balance) information from the inner ear to the b ...

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 Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...

Causes

Leptomeningeal carcinomatosis occurs when the cancer cells invade the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

and spread throughout the central nervous system. The metastatic tumor cells grow either attached to the

pia mater Pia mater ( or ),Entry "pia mater"
in
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

and

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...

or floating unattached to the subarachnoid space. Tumors of diverse origins and hematologic cancers may spread to this space. Some patients can develop a leptomeningeal tumor while receiving chemotherapy for their primary tumor.

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

. 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

. 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

. 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 The cranial cavity, also known as intracranial space, is the space within the skull that accommodates the brain. The skull minus the mandible is called the ''cranium''. The cavity is formed by eight cranial bones known as the neurocranium that in ...

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

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...

al swelling. In areas of tumor cells, infiltration of

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

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 A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency i ...

, 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.

From primary cancer to the meninges

NM is a secondary cancer meaning that it is the result of

neoplastic A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

cells that have

metastasized Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

from a primary cancer site. These cancers develop an enzyme that is able to break down blood vessels at a microscopic level. These cells enter the blood vessels and travel across the body. Once the brain is reached, they break down the blood–brain barrier to enter the

Cerebrospinal Fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

(CSF). There the cancerous cells seed and disseminate into the

which are composed of the

arachnoid Arachnoid may refer to: * Relating to arachnids * Arachnoid (astrogeology), a geological structure found only on the planet Venus * Arachnoid (botany), referring to organs with a cobwebby exterior appearance * Arachnoid granulation, small protrus ...

and the pia. The CSF continues to carry neoplastic cells through the brain tracts and spreads the cancerous cells.

Lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malign ...

, and

malignant melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ...

comprise the majority of solid tumors spreading to the leptomeninges. Although rare, meningeal carcinomatosis can arise from cervical cancer. Only eight cases of MC arising from squamous cell carcinoma of the uterine cervix are previously reported in the literature. Since NM is a result of primary cancer metastasis and can develop from primary brain tumors or

parenchymal Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the word ...

metastasis when tumor cells are lodged in small

(CNS)

vasculature The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

, causing local ischemia and vessel damage which result in tumor spillage into the

Virchow-Robin spaces A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain blood vessels in several organs, including the brain, potentially having an immunological function, but more broadly a dispersive role for ...

and providing access to the subarachnoid space.

Invasion routes

* Hematogenous spread, or spread through blood vessels, occurs either through the

venous plexus In vertebrates, a venous plexus is a normal congregation anywhere in the body of multiple veins. A list of venous plexuses: * Basilar plexus * Batson venous plexus * Internal vertebral venous plexuses * Pterygoid plexus * Submucosal venous ...

of Batson or by arterial dissemination. This occurs with

arterioles An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries. Arterioles have muscular walls (usually only one to two layers of smooth muscle cells) and are the primar ...

as a result of tumor cells being lodged in vessels that feed the meninges and later causing leakage into the meninges and CSF. This same situation also appear with spinal arteries where leakage of tumor cells is into the

nerve roots A nerve root (Latin: ''radix nervi'') is the initial segment of a nerve leaving the central nervous system. Nerve roots can be classified as: *Cranial nerve roots: the initial or proximal segment of one of the twelve pairs of cranial nerves leaving ...

. More regarding the effects of NM on spinal cord is discussed later. Tumor cells may also seed the

choroid plexus The choroid plexus, or plica choroidea, is a plexus of cells that arises from the tela choroidea in each of the ventricles of the brain. Regions of the choroid plexus produce and secrete most of the cerebrospinal fluid (CSF) of the central nerv ...

, where CSF is produced, and ultimately gaining direct access to the CSF. Seeding of the

is most common in patients with third and lateral ventricular hydrocephalus. * Venous spread may occur when intra-abdominal or

thoracic pressure The thoracic diaphragm, or simply the diaphragm ( grc, διάφραγμα, diáphragma, partition), is a sheet of internal skeletal muscle in humans and other mammals that extends across the bottom of the thoracic cavity. The diaphragm is the mo ...

increases and venous flow is retrograde which then allows tumor cells in the systemic

venous Veins are blood vessels in humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated ...

system to enter the vertebral venous system. * Centripetal migration from systemic tumors along perineural, invasion of nerve space, or

perivascular Mural cells are the vascular smooth muscle cells (vSMCs), and pericytes, of the microcirculation. Both types are in close contact with the endothelial cells lining the capillaries, and are important for vascular development and stability. Mural cel ...

spaces. Malignant cells can migrate along spinal or cranial nerve

epineurium The epineurium is the outermost layer of dense irregular connective tissue surrounding a peripheral nerve. It usually surrounds multiple nerve fascicles as well as blood vessels which supply the nerve. Smaller branches of these blood vessels pe ...

perineurium The perineurium is a protective sheath that surrounds a nerve fascicle. This bundles together axons targeting the same anatomical location. The perineurium is composed from fibroblasts. In the peripheral nervous system, the myelin sheath of each ...

, invade the subpial space, and travel along blood vessels into the endoneurial space, or invade the nerve parenchyma. Infiltration happens most often at the base of the brain, dorsal surface, and especially at the

cauda equina The cauda equina () is a bundle of spinal nerves and spinal nerve rootlets, consisting of the second through fifth lumbar nerve pairs, the first through fifth sacral nerve pairs, and the coccygeal nerve, all of which arise from the lumbar enlarg ...

, which is largely due to the effect of gravity. Once in the CSF, malignant cells can extend along the membrane surfaces or spread freely in the CSF and attach to other locations. These cells have the ability to penetrate the pial membrane and invade the spinal cord and

cranial nerves Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...

Infiltration to spinal cord

Infiltration from the subarachnoid space into the spinal cord occurs primarily along the perivascular tissues that surround blood vessels at the brain entrance. Infiltration from the anterior median fissure, a 3mm deep furrow on the anterior side of the spinal cord, to the anterior horn of the spinal cord, the ventral grey matter of the spinal cord, is found along the central artery. Direct infiltration of the nerve roots is also observed, mostly from the

dorsal roots The dorsal root of spinal nerve (or posterior root of spinal nerve or sensory root) is one of two "roots" which emerge from the spinal cord. It emerges directly from the spinal cord, and travels to the dorsal root ganglion. Nerve fibres with the v ...

(the afferent sensory root of the spinal nerve) than the

ventral roots In anatomy and neurology, the ventral root of spinal nerve, anterior root, or motor root is the efferent motor root of a spinal nerve. At its distal end, the ventral root joins with the dorsal root The dorsal root of spinal nerve (or posterior ...

(the efferent motor root of a spinal nerve). With mild infiltration, tumor cells are found diffusely in the subarachnoid space from the

cervical In anatomy, cervical is an adjective that has two meanings: # of or pertaining to any neck. # of or pertaining to the female cervix: i.e., the ''neck'' of the uterus. *Commonly used medical phrases involving the neck are **cervical collar **cerv ...

sacral Sacral may refer to: *Sacred Sacred describes something that is dedicated or set apart for the service or worship of a deity; is considered worthy of spiritual respect or devotion; or inspires awe or reverence among believers. The property ...

levels. In some cases however there are no differences between spine levels. Infiltration from the subarachnoid space into the spinal cord occurs mainly along the perivascular space of the

white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distributi ...

. However, in some cases, direct infiltration into the spinal cord parenchyma is found together with destruction of the pia mater.

Diagnosis

Screening involves an MRI scan to identify and diagnose tumors in the subarachnoid region of the brain. MRI can make a diagnosis even without an analysis of the cerebrospinal fluid but it can sometimes be difficult to detect because MRI scans cannot always pick up the problem. Diagnosis is most commonly made by lumbar puncture to detect malignant cells in the CSF, although the tests may be negative in roughly 10% of patients. Diagnosis often requires a high index of suspicion and is confirmed by neuroimaging and cerebrospinal fluid analysis. CSF examination is the most useful diagnostic tool for NM. Patients with suspected NM should undergo one or two lumbar punctures, cranial magnetic resonance imaging (MRI), spinal MRI, and a

radioisotope A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess nuclear energy, making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferr ...

CSF flow study to rule out sites of CSF block. If the

cytology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...

remains negative and radiological studies are not definitive, consideration may be given to ventricular or lateral cervical spine CSF analysis based on the suspected site of predominant disease. Consideration of signs, symptoms, and neuroimaging can help with the placement to where CSF is drawn. Median time of diagnosis from initial primary cancer diagnosis is between 76 days and 17 months.

Difficulties in diagnosis

NM is multifocal and CSF at a particular site may show no abnormalities if the pathological site is far away. Only 50% of those suspected with NM are actually diagnosed with NM and only the presence of malignant cells in the CSF is diagnosis conclusive.

Techniques

* MRI: Meningeal findings are described with the following characteristics: Nodular meningeal tumor, meningeal thickening >3 mm and a subjectively strong contrast enhancement. A smooth contrast enhancement of the meninges was judged to be typical for inflammatory, nonneoplastic meningitis. * CSF cytology: is performed after drawing the CSF by lumbar puncture. * Cytogenetic: measures

chromosomal A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

content of cells and

fluorescence Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation. It is a form of luminescence. In most cases, the emitted light has a longer wavelength, and therefore a lower photon energy, tha ...

in situ ''In situ'' (; often not italicized in English) is a Latin phrase that translates literally to "on site" or "in position." It can mean "locally", "on site", "on the premises", or "in place" to describe where an event takes place and is used in ...

hybridization which detects numerical and structural genetic aberrations as a sign of malignancy. This is especially useful for liquid tumors such as

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

and

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...

. Some of the techniques that achieve this are flow cytometry and DNA single-cell cytometry. However, cytogenetic only assist in diagnosis and is less preferred. * Meningeal

Biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...

: may be performed when all of the above criteria is inconclusive. Biopsy is only effective when performed at the region where there's enhancement on the MRI.

Cerebral spinal fluid

Criteria for CSF abnormalities include: * Increased opening pressure (> 200mm of H2O) * Increased Leukocytes (>4/mm3) * Elevated protein (>50 mg/dL) * Decreased glucose (<60 mg/dL)

Tumor markers

These markers can be good indirect indicator of NM but most are not sensitive enough to improve cytogical diagnosis: * Carcinoembryonic antigen (CEA) *

alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...

* beta-

human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantatio ...

* carbohydrate antigen19-9 * creatine-kinase BB *

isoenzyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...

* tissue polypeptide antigen *

Beta-2 microglobulin β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells (excluding red blood cells). In humans, the β2 microglobulin protein is encoded by th ...

* beta-glucoronidase * lactate dehydrogenase isoenzyme-5 *

vascular endothelial growth factor Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...

Treatment

There is currently no cure for leptomeningeal disease as the tumor is hard to eradicate. Current treatments for leptomeningeal tumors are palliative. The goals for treatment include prolonging survival and stabilizing neurological symptoms.

Radiotherapy

Radiotherapy is used mostly for focal type of NM due to the nature of damage and success rate associated with the treatment. Radiotherapy targets the tumor and destroys the collective tissues of cancerous cells.

Chemotherapy

Chemotherapy is injected directly into the cerebrospinal fluid, either by lumbar puncture (“spinal tap”) or through a surgically implanted device called an

Ommaya reservoir An Ommaya reservoir is an intraventricular catheter system that can be used for the aspiration of cerebrospinal fluid or for the delivery of drugs (e.g. chemotherapy) into the cerebrospinal fluid. It consists of a catheter in one lateral ventricle ...

. Intrathecal Therapy is preferred since intravenous chemotherapy do not penetrate the BBB. The most common chemicals used are

liposomal A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug deliver ...

cytarabine Cytarabine, also known as cytosine arabinoside (ara-C), is a chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma. It is given by i ...

(DepoCyte) and intrathecal methotrexate (MTX). The downside of a spinal tap diagnosis is that while it is highly accurate and reliable, it can also report false-negative results. Chemotherapy is delivered intrathecally as it is hard for drugs to make it into the central nervous system. Intrathecal chemotherapy can only penetrate a few millimeters. If the tumor is any thicker, radiation is given to shrink it down. The treatment is done to reduce pressure on the brain caused by any

buildup and to reduce the number of cancer cells causing the pressure. For the best care, patients should see a physician who regularly treats leptomeningeal cancer and is most up-to-date on medicines that penetrate the blood-brain barrier, how to treat the symptoms, and clinical trials that might include patients with leptomeningeal cancer.

Risks of treatments

Both Chemotherapy and Radiotherapy are harmful to the body and most definitely the brain. Caution must be utilized in treating patients with NM. Another factor that makes treatment difficult is that there is no suitable method to evaluate the disease progression.

Prognosis

The prognosis is generally poor with survival typically measured in months. The median survival time of patients without treatment is four to six weeks. The best prognoses are seen from NM due to breast cancer with the median overall survival of no more than six months after diagnosis of NM. Death is generally due to progressive neurological dysfunction. Treatment is meant to stabilize neurological function and prolong survival. Neurological dysfunction usually cannot be fixed but progressive dysfunction can be halted and survival may be increased to four to six months. It occurs in approximately 3-5% of cancer patients. The disease is usually terminal and if left untreated, the median survival is 4–6 weeks whereas if treated, the median survival can increase to 2–3 months. Treatment will be more effective if it is done on the primary tumor before it metastasizes to the brain or spinal cord. Patients with

leukaemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

achieve better results compared to patients with solid tumours who have undergone treatment. It was found that 75% of patients stabilize or improve over several months as opposed to 25% of patients who do not respond and have progressive disease. But despite initial improvement, most patients survive only a few months. Breast cancer and small cell lung cancer are the two solid tumors that respond best to treatment Some patients do better than others, particularly those whose primary cancer is hematologic, bone marrow and lymph nodes.

Factors that lower survival

Much of prognosis can be determined from the damage due to primary cancer. Negative

hormone receptor A hormone receptor is a receptor molecule that binds to a specific chemical messenger . Hormone receptors are a wide family of proteins made up of receptors for thyroid and steroid hormones, retinoids and Vitamin D, and a variety of other recepto ...

status, poor performance status, more than 3 chemotherapy regimes, and high Cyfra 21-1 level at diagnosis, all indicates lower survival period of patients with NM. Cyfra 21-1 is a fragment of the

cytokeratin Cytokeratins are keratin proteins found in the intracytoplasmic cytoskeleton of epithelial tissue. They are an important component of intermediate filaments, which help cells resist mechanical stress. Expression of these cytokeratins within epi ...

19 and may reflect the tumor burden within the CSF.

Epidemiology

In the United States, 1–8% of cancer patients are diagnosed with leptomeningeal disease, with approximately 110,000 cases per year. The exact incidence of leptomeningeal disease is difficult to determine, since gross examination at autopsy may overlook signs of leptomeningeal disease, and microscopic pathological inspection may be normal if the seeding is multifocal or if an unaffected area of the

(CNS) is examined.

Current research

New treatments and clinical trial for breast cancer patients and non-small cell lung cancer patients with leptomeningeal disease are currently being explored. People with leptomeningeal metastasis are generally excluded from clinical trials, thereby limiting the systematic assessment of novel therapies in this subgroup of patients with poor prognosis. More patients with leptomeningeal metastasis should be enrolled into trials investigating novel agents with the potential to penetrate the blood–brain barrier. Novel approaches are being studied as currently available therapies are toxic and provide limited benefits.

History

Neoplastic Meningitis (NM) was first reported in the 1870s.Herrlinger (2004). Leptomeningeal metastasis: survival and prognostic factors in 155 patients. Journal of the Neurological Sciences, 223(2), 167-178. doi: 10.1016/j.jns.2004.05.008

Gallery

File:Meningeosis carcinomatosa bei Mamma-Ca - fokal - MRT T1 KM axial.jpg, Meningeal carcinomatosis in a patient with breast cancer (contrast-enhanced axial T1-weighted MRI)

References

External links

{{Commons category, Meningeal carcinomatosis Nervous system neoplasia