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| ==[[Neoplastic meningitis overview|Overview]]== | | ==[[Neoplastic meningitis overview|Overview]]== |
| * Neoplastic meningitis is a secondary cancer of the subarachnoid space, meninges and pia matter from a primary tumor source. It could be from a distant metastasis or from a primary brain tumor. Most commonly documented primary distant source is beast cancer. Signs and symptoms vary widely depending on the site of the brain or spinal cord involved and is not necessarily limited to signs of meningeal irritation. Neoplastic meningitis have a very poor prognosis with survival limited to 4 - 6 weeks if left untreated and 2 - 6 months with palliative management. Treatment if 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093424/]
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| ==[[Neoplastic meningitis historical perspective|Historical Perspective]]== | | ==[[Neoplastic meningitis historical perspective|Historical Perspective]]== |
| * The first case of neoplastic meningitis was described by Eberth in the 1870s.
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| | ==[[Neoplastic meningitis classification|Classification]]== |
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| ==[[Neoplastic meningitis classification|Classification]]==
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| ==[[Neoplastic meningitis pathophysiology|Pathophysiology]]== | | ==[[Neoplastic meningitis pathophysiology|Pathophysiology]]== |
| * The pathophysiology of neoplastic meningitis involves spread of cancer cells to the meninges and subarachnoid space. The location could be the brain or the spinal cord. It could be from a distant source or from a primary CNS tumor (drop metastasis).
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| * Cancer from a distant source enter the CSF by means of the following:[https://en.wikipedia.org/wiki/Neoplastic_meningitis]
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| ** Hematogenous Spread from 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.
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| ** 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 spaces thereby providing access to the subarachnoid space.
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| ** 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.
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| ** 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.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093424/]
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| ** Iatrogenic - from surgical procedures involving removal of a primary brain tumor
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| * Primary neoplastic meningitis has also been documented particularly with melanoma.[https://moffitt.org/media/6005/22.pdf]
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| ==[[Neoplastic meningitis causes|Causes]]== | | ==[[Neoplastic meningitis causes|Causes]]== |
| * Neoplastic meningitis is a secondary cancer caused by the spread of tumor cells into the meninges and subarachnoid space from a primary source. Most common solid tumor sources documented are breast, lung, melanoma and hematologic cancers mostly acute lymphocytic leukemia. Cancers not previously thought to be predisposed to neoplastic meningitis but now has documented cases are gastric, prostate, ovarian, cervical and endometrial. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093424/]
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| ==[[Neoplastic meningitis differential diagnosis|Differentiating Neoplastic Meningitis from other Diseases]]== | | ==[[Neoplastic meningitis differential diagnosis|Differentiating Xyz from other Diseases]]== |
| * Differential Diagnosis for Neoplastic Meningitis:
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| # Meningitis from infectious causes - infectious meningitis may to some degree manifest like neoplastic meningitis due to meningeal irritation. This include viral, bacterial, fungal and HIV-associated causes of meningitis.
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| # Neurosarcoidosis
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| # Vasculitis - the generalized nature of vessel involvement in these diseases may, to some extent involve the meninges. Vasculitis documented to present like neoplastic meningitis include Kawasaki disease, Takayasu arteritis, Polyarteritis nodosa, microscopic polyarteritis nodosa and Wegener granulomatosis.
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| # Systemic Connective Tissue Diseases - SLE, Sjogrens syndrome.
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| ==[[Neoplastic meningitis epidemiology and demographics|Epidemiology and Demographics]]== | | ==[[Neoplastic meningitis epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==[[Neoplastic meningitis risk factors|Risk Factors]]== | | ==[[Neoplastic meningitis risk factors|Risk Factors]]== |
| * Factors that have been known to increase the risk of neoplastic meningitis involves:[https://moffitt.org/media/6005/22.pdf]
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| ** Brain surgery - higher incidence of neoplastic meningitis has been observed after resection of brain tumor (particularly piecemeal resection vs en-block resection) particularly tumors located in the cerebellum.
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| ** ER-, PR-positivity - presence of these receptors in beast cancer increases incidence of neoplastic meningitis. Triple negative breast cancer is associated with very little risk for neoplastic meningitis and the HER2/neu gene positivity is not linked with neoplastic meningitis.
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| ==[[Neoplastic meningitis screening|Screening]]== | | ==[[Neoplastic meningitis screening|Screening]]== |
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| ==[[Neoplastic meningitis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== | | ==[[Neoplastic meningitis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| * Neoplastic meningitis occur in about 5% of people with cancer. It is usually one of the dreaded complications of malignancy as it is terminal and treatment has been established to be palliative management. [https://emedicine.medscape.com/article/1156338-overview] Autopsy shows that neoplastic meningitis is present is about 19-25% of the cases of malignant disease
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| * 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%)[https://theoncologist.alphamedpress.org/content/13/9/967.full]
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| * Symptoms are often multifocal and neuraxal. The most common presenting symptom of neoplastic meningitis is pain or seizure. [https://emedicine.medscape.com/article/1156338-overview]
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| * 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.[https://moffitt.org/media/6005/22.pdf]
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| * 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.[http://theoncologist.alphamedpress.org/content/13/9/967.full]
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| ==Diagnosis== | | ==Diagnosis== |
| [[Neoplastic meningitis staging|Staging]] | [[Neoplastic meningitis history and symptoms|History and Symptoms]] | [[Neoplastic meningitis physical examination|Physical Examination]] | [[Neoplastic meningitis laboratory tests|Laboratory Findings]] | [[Neoplastic meningitis CT|CT]] | [[Neoplastic meningitis MRI|MRI]] | [[Neoplastic meningitis other imaging findings|Other Imaging Findings]] | [[Neoplastic meningitis other diagnostic studies|Other Diagnostic Studies]] | | [[Neoplastic meningitis diagnostic study of choice|Diagnostic study of choice]] | [[Neoplastic meningitis history and symptoms|History and Symptoms]] | [[Neoplastic meningitis physical examination|Physical Examination]] | [[Neoplastic meningitis laboratory tests|Laboratory Findings]] | [[Neoplastic meningitis X-ray|X-Ray Findings]] | [[Neoplastic meningitis echocardiography and ultrasound|Echocardiography and Ultrasound]] | [[Neoplastic meningitis CT|CT-Scan Findings]] | [[Neoplastic meningitis MRI|MRI Findings]] | [[Neoplastic meningitis other imaging findings|Other Imaging Findings]] | [[Xyz other diagnostic studies|Other Diagnostic Studies]] |
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| ==Treatment== | | ==Treatment== |
| [[Neoplastic meningitis medical therapy|Medical Therapy]] | [[Neoplastic meningitis surgery|Surgery]] | [[Neoplastic meningitis prevention|Prevention]] | [[Neoplastic meningitis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Neoplastic meningitis future or investigational therapies|Future or Investigational Therapies]] | | [[Neoplastic meningitis medical therapy|Medical Therapy]] | [[Neoplastic meningitis surgery|Surgery]] | [[Neoplastic meningitis primary prevention|Primary Prevention]] | [[Neoplastic meningitis secondary prevention|Secondary Prevention]] | [[Neoplastic meningitis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Neoplastic meningitis future or investigational therapies|Future or Investigational Therapies]] |
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| ==Case Studies== | | ==Case Studies== |