Neoplastic meningitis overview: Difference between revisions
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==Overview== | ==Overview== | ||
Neoplastic meningitis is the development of [[meningitis]] due to infiltration of the [[subarachnoid space]] by tumor cells. | Neoplastic meningitis is the development of [[meningitis]] due to infiltration of the [[subarachnoid space]] by tumor cells. Neoplastic meningitis was first reported in the 1870's.<ref name="overviewnm1">Neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 19, 2016</ref> Neoplastic meningitis refers to the spread of malignant cells through the [[cerebrospinal fluid]] space. These cells can be originated both in primary CNS tumors (e.g. drop-metastases), as well as from distant tumors that have metastasized (hematogenous spread).<ref name="nm1introduction">Leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 20, 2016</ref> The microscopic pathology of neoplastic meningitis may vary according to the primary cancer involved. Generally, on microscopic histopathological analysis, neoplastic meningitis is characterized by large, hyperchromatic cells.<ref name="BerzeroDiamanti2015">{{cite journal|last1=Berzero|first1=Giulia|last2=Diamanti|first2=Luca|last3=Di Stefano|first3=Anna Luisa|last4=Bini|first4=Paola|last5=Franciotta|first5=Diego|last6=Imarisio|first6=Ilaria|last7=Pedrazzoli|first7=Paolo|last8=Magrassi|first8=Lorenzo|last9=Morbini|first9=Patrizia|last10=Farina|first10=Lisa Maria|last11=Bastianello|first11=Stefano|last12=Ceroni|first12=Mauro|last13=Marchioni|first13=Enrico|title=Meningeal Melanomatosis: A Challenge for Timely Diagnosis|journal=BioMed Research International|volume=2015|year=2015|pages=1–6|issn=2314-6133|doi=10.1155/2015/948497}}</ref> Common causes of neoplastic meningitis include primary [[brain tumor|intracerebral malignancies]] ([[glioblastoma multiforme]], [[anaplastic astrocytoma]], [[medulloblastoma]]) and metastatic disease ([[breast cancer]], [[lung cancer]], [[melanoma]], [[lymphoma]], [[leukemia]]).<ref name="causes1">Pathology of leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 19, 2016</ref> Neoplastic meningitis must be differentiated from infections ([[meningitis]], [[Lyme disease]], [[neurocysticercosis]]), neoplastic ([[intracerebral metastasis]], dural metastasis), inflammatory ([[rheumatoid arthritis]], [[multiple sclerosis]], [[polychondritis]]), and granulomatous disorders ([[sarcoidosis]], [[histiocytosis]], [[Wegener's granulomatosis]], [[vasculitis]]).<ref name="ddxmeningitis">Leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> Neoplastic meningitis occurs in approximately 3-5% of patients with solid tumor, 5-15% of patients with leukemia, and 1-2% of patients with primary brain tumors.<ref name="GleissnerChamberlain2006">{{cite journal|last1=Gleissner|first1=Beate|last2=Chamberlain|first2=Marc Charles|title=Neoplastic meningitis|journal=The Lancet Neurology|volume=5|issue=5|year=2006|pages=443–452|issn=14744422|doi=10.1016/S1474-4422(06)70443-4}}</ref><ref name="epidemiologynm2">Hayat, M. A. Brain metastases from primary tumors : epidemiology, biology, and therapy. London: Elsevier/Academic Press, 2014. Print.| url=https://books.google.com/books?id=IloXAwAAQBAJ&pg=PA43&lpg=PA43&dq=leptomeningeal+carcinomatosis+is+present+in+1-5%25+of+patients+with+solid+tumors,+5-15%25+of+patients+with+leukemia,+and+1-2%25+of+patients+with+primary+brain+tumors.&source=bl&ots=ehEaDBCT5f&sig=vvSxdxDjNMBe0CdCP6fEcMaYJqU&hl=en&sa=X&ved=0ahUKEwi2ueuw37bKAhUG8j4KHWUUCoIQ6AEILTAC#v=onepage&q=leptomeningeal%20carcinomatosis%20is%20present%20in%201-5%25%20of%20patients%20with%20solid%20tumors%2C%205-15%25%20of%20patients%20with%20leukemia%2C%20and%201-2%25%20of%20patients%20with%20primary%20brain%20tumors.&f=false. Accessed on January 19, 2016</ref> Neoplastic meningitis has a widely disseminated and progressive presentation. If left untreated, neoplastic meningitis may progress to develop [[seizures]], [[hydrocephalus]], [[encephalopathy]], and ultimately death.<ref name="dcomplicationsnm1">Complications of leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> Complications of neoplastic meningitis include [[hydrocephalus]], [[encephalopathy]], [[empyema]], [[cerebritis]], [[cerebral abscess]], and [[stroke]].<ref name="dcomplicationsnm1">Complications of leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> The median survival time of patients without treatment of neoplastic meningitis is 4-6 weeks.<ref name="prognosisnm123">Prognosis of neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 20, 2016</ref> Neoplastic meningitis should be suspected if there are simultaneous occurrence of symptoms or signs in more than one area of the [[neuraxis]].<ref>{{cite journal|title=Infiltration of the Leptomeninges by Systemic Cancer-A Clinical and Pathologic Study|doi=10.1001/archneur.1974.00490320010002.}}</ref> Symptoms of neoplastic meningitis include [[headaches]], [[confusion]], [[memory loss]], [[seizures]], [[diplopia|double vision]], [[hearing loss]], [[paresthesia]] and [[pain]] in the neck and back, and limb weakness.<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> Common physical examination findings of neoplastic meningitis include [[altered mental status]], [[dementia]], [[hemiparesis]], [[ptosis]], [[nuchal rigidity]], bowel and bladder dysfunction, and [[papilledema]].<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> Laboratory findings consistent with the diagnosis of neoplastic meningitis include abnormal CSF analysis (increased opening pressure, increased leukocytes, elevated protein, decreased glucose, and positive tumor markers). Only 50% of those suspected with neoplastic meningitis are actually diagnosed and only the '''presence of malignant cells in the CSF''' is diagnostic.<ref name="dxnm123">Diagnosis of neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 20, 2016</ref> Brain MRI is helpful in the diagnosis of neoplastic meningitis. On MRI, neoplastic meningitis is characterized by normal T1- and T2-weighted images. On contrast administration, there may be leptomeningeal enhancement scattered over the brain in a 'sugar coated' manner, which is fairly diagnostic for neoplastic meningitis.<ref name="eaturesradiographicfneomeningitis1">Radiographic features of leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 19, 2016</ref> Other diagnostic studies for neoplastic meningitis include [[biopsy|meningeal biopsy]], which may be diagnostic if there are no systemic manifestations and the CSF analysis remain inconclusive.<ref name="AhnLim2013">{{cite journal|last1=Ahn|first1=Shin|last2=Lim|first2=Kyung Soo|title=Three Cases of Neoplastic Meningitis Initially Diagnosed with Infectious Meningitis in Emergency Department|journal=Case Reports in Emergency Medicine|volume=2013|year=2013|pages=1–4|issn=2090-648X|doi=10.1155/2013/561475}}</ref> The mainstay of therapy for neoplastic meningitis is [[intrathecal chemotherapy]].<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> [[Radiotherapy]] may be used in patients with neoplastic meningitis for palliation of symptoms, reduce the bulky tumors, and correction of cerebrospinal fluid flow abnormalities.<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> Supportive care should be directed towards all patients with neoplastic meningitis, regardless of the treatment regimen ([[anticonvulsants]], [[corticosteroids]], and [[opiates]]).<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> [[Surgery]] is not the first-line treatment option for patients with neoplastic meningitis. Surgery is usually reserved for patients who need an intraventricular catheter placement for administration of cytotoxic drugs or placement of a ventriculoperitoneal shunt in patients with [[hydrocephalus|symptomatic hydrocephalus]].<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | ||
==Historical Perspective== | ==Historical Perspective== | ||
* The first case of neoplastic meningitis was described by Eberth in the 1870s. | |||
==Classification== | ==Classification== | ||
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==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). | |||
* Cancer from a distant source enter the CSF by means of the following:[https://en.wikipedia.org/wiki/Neoplastic_meningitis] | |||
** [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1459485/ 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 [https://en.wikipedia.org/wiki/Batson_venous_plexus Batsons venous plexus]. | |||
** 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 [https://en.wikipedia.org/wiki/Perivascular_space Virchow-Robin spaces] thereby providing access to the [https://radiopaedia.org/articles/subarachnoid-space subarachnoid space]. | |||
** 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. | |||
** 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.[5] | |||
** Iatrogenic - from surgical procedures involving removal of a primary brain tumor | |||
* Primary neoplastic meningitis has also been documented particularly with melanoma.<ref>{{Cite web|url=https://moffitt.org/media/6005/22.pdf|title=Neoplastic Meningitis due to Lung, Breast and Melanoma Metastases|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref> | |||
==Causes== | ==Causes== | ||
Common causes of neoplastic meningitis include primary [[brain tumor|intracerebral malignancies]] ([[glioblastoma multiforme]], [[anaplastic astrocytoma]], [[medulloblastoma]]) and metastatic disease ([[breast cancer]], [[lung cancer]], [[melanoma]], [[lymphoma]], [[leukemia]]).<ref name=causes1>Pathology of leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 19, 2016</ref> | |||
* Common causes of neoplastic meningitis include primary [[brain tumor|intracerebral malignancies]] ([[glioblastoma multiforme]], [[anaplastic astrocytoma]], [[medulloblastoma]]) and metastatic disease ([[breast cancer]], [[lung cancer]], [[melanoma]], [[lymphoma]], [[leukemia]]).<ref name="causes1">Pathology of leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 19, 2016</ref> | |||
==Differentiating Neoplastic Meningitis from other Diseases== | ==Differentiating Neoplastic Meningitis from other Diseases== | ||
Neoplastic meningitis must be differentiated from infections ([[meningitis]], [[Lyme disease]], [[neurocysticercosis]]), neoplastic ([[intracerebral metastasis]], dural metastasis), inflammatory ([[rheumatoid arthritis]], [[multiple sclerosis]], [[polychondritis]]), and granulomatous disorders ([[sarcoidosis]], [[histiocytosis]], [[Wegener's granulomatosis]], [[vasculitis]]).<ref name=ddxmeningitis>Leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> | |||
* Neoplastic meningitis must be differentiated from infections ([[meningitis]], [[Lyme disease]], [[neurocysticercosis]]), neoplastic ([[intracerebral metastasis]], dural metastasis), inflammatory ([[rheumatoid arthritis]], [[multiple sclerosis]], [[polychondritis]]), and granulomatous disorders ([[sarcoidosis]], [[histiocytosis]], [[Wegener's granulomatosis]], [[vasculitis]]).<ref name="ddxmeningitis">Leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> | |||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
Neoplastic meningitis occurs in approximately 3-5% of patients with solid tumor, 5-15% of patients with leukemia, and 1-2% of patients with primary brain tumors.<ref name="GleissnerChamberlain2006">{{cite journal|last1=Gleissner|first1=Beate|last2=Chamberlain|first2=Marc Charles|title=Neoplastic meningitis|journal=The Lancet Neurology|volume=5|issue=5|year=2006|pages=443–452|issn=14744422|doi=10.1016/S1474-4422(06)70443-4}}</ref><ref name=epidemiologynm2>Hayat, M. A. Brain metastases from primary tumors : epidemiology, biology, and therapy. London: Elsevier/Academic Press, 2014. Print.| url=https://books.google.com/books?id=IloXAwAAQBAJ&pg=PA43&lpg=PA43&dq=leptomeningeal+carcinomatosis+is+present+in+1-5%25+of+patients+with+solid+tumors,+5-15%25+of+patients+with+leukemia,+and+1-2%25+of+patients+with+primary+brain+tumors.&source=bl&ots=ehEaDBCT5f&sig=vvSxdxDjNMBe0CdCP6fEcMaYJqU&hl=en&sa=X&ved=0ahUKEwi2ueuw37bKAhUG8j4KHWUUCoIQ6AEILTAC#v=onepage&q=leptomeningeal%20carcinomatosis%20is%20present%20in%201-5%25%20of%20patients%20with%20solid%20tumors%2C%205-15%25%20of%20patients%20with%20leukemia%2C%20and%201-2%25%20of%20patients%20with%20primary%20brain%20tumors.&f=false. Accessed on January 19, 2016</ref> | |||
* Neoplastic meningitis occurs in approximately 3-5% of patients with solid tumor, 5-15% of patients with leukemia, and 1-2% of patients with primary brain tumors.<ref name="GleissnerChamberlain2006">{{cite journal|last1=Gleissner|first1=Beate|last2=Chamberlain|first2=Marc Charles|title=Neoplastic meningitis|journal=The Lancet Neurology|volume=5|issue=5|year=2006|pages=443–452|issn=14744422|doi=10.1016/S1474-4422(06)70443-4}}</ref><ref name="epidemiologynm2">Hayat, M. A. Brain metastases from primary tumors : epidemiology, biology, and therapy. London: Elsevier/Academic Press, 2014. Print.| url=https://books.google.com/books?id=IloXAwAAQBAJ&pg=PA43&lpg=PA43&dq=leptomeningeal+carcinomatosis+is+present+in+1-5%25+of+patients+with+solid+tumors,+5-15%25+of+patients+with+leukemia,+and+1-2%25+of+patients+with+primary+brain+tumors.&source=bl&ots=ehEaDBCT5f&sig=vvSxdxDjNMBe0CdCP6fEcMaYJqU&hl=en&sa=X&ved=0ahUKEwi2ueuw37bKAhUG8j4KHWUUCoIQ6AEILTAC#v=onepage&q=leptomeningeal%20carcinomatosis%20is%20present%20in%201-5%25%20of%20patients%20with%20solid%20tumors%2C%205-15%25%20of%20patients%20with%20leukemia%2C%20and%201-2%25%20of%20patients%20with%20primary%20brain%20tumors.&f=false. Accessed on January 19, 2016</ref> | |||
==Risk Factors== | ==Risk Factors== | ||
* Factors that have been known to increase the risk of neoplastic meningitis involves:[https://moffitt.org/media/6005/22.pdf] | |||
** Brain metastasis is one of the more obvious risk factors for neoplastic meningitis. Coexisting brain metastasis are associated with neoplastic meningitis in breast cancer (33-54%), lung cancer (56-82%) and melanoma (87-96%). | |||
** [https://www.webmd.com/cancer/brain-cancer/brain-tumor-types#1 Primary brain cancer] always poses a risk for the development of neoplastic meningitis. It is diagnosed in 1-2% of cases of ependymoma, medulloblastoma, germinoma and glioblastoma combined. | |||
** Brain surgery increases the chance of developing neoplastic meningitis. It has been observed after resection of brain tumor (particularly piecemeal resection vs en-block resection) particularly tumors located in the cerebellum. Other cranial surgeries done with involvement of ventricular system manipulation in a patient with known brain metastasis increases the risk. Furthermore, the incidence of neoplastic meningitis seem higher in patient treated with surgery followed by stereotactic radiosurgery compared with radiosurgery alone. | |||
** ER-, PR-positivity in beast cancer increases incidence of neoplastic meningitis. Triple negative breast cancer and the HER2/neu gene positivity displays tropism for CNS metastasis. Among the histologic subtypes of breast cancer, loblular carcinoma demonstrated the highest prevalence for neoplastic meningitis. | |||
<br /> | |||
==Screening== | ==Screening== | ||
There is insufficient evidence to recommend routine screening for neoplastic meningitis.<ref name=screen>Early detection, diagnosis, and staging of brain tumors. American cancer society. http://www.cancer.org/cancer/braincnstumorsinadults/detailedguide/brain-and-spinal-cord-tumors-in-adults-detection</ref> | |||
* There is insufficient evidence to recommend routine screening for neoplastic meningitis.<ref name="screen">Early detection, diagnosis, and staging of brain tumors. American cancer society. http://www.cancer.org/cancer/braincnstumorsinadults/detailedguide/brain-and-spinal-cord-tumors-in-adults-detection</ref> | |||
==Natural History, Complications and Prognosis== | ==Natural History, Complications and Prognosis== | ||
Neoplastic meningitis has a widely disseminated and progressive presentation. If left untreated, neoplastic meningitis may progress to develop [[seizures]], [[hydrocephalus]], [[encephalopathy]], and ultimately death.<ref name=dcomplicationsnm1>Complications of leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> Complications of neoplastic meningitis include [[hydrocephalus]], [[encephalopathy]], [[empyema]], [[cerebritis]], [[cerebral abscess]], and [[stroke]].<ref name=dcomplicationsnm1>Complications of leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> The median survival time of patients without treatment of neoplastic meningitis is 4-6 weeks.<ref name=prognosisnm123>Prognosis of neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 20, 2016</ref> | |||
* Neoplastic meningitis has a widely disseminated and progressive presentation. If left untreated, neoplastic meningitis may progress to develop [[seizures]], [[hydrocephalus]], [[encephalopathy]], and ultimately death.<ref name="dcomplicationsnm1">Complications of leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> | |||
* Complications of neoplastic meningitis include [[hydrocephalus]], [[encephalopathy]], [[empyema]], [[cerebritis]], [[cerebral abscess]], and [[stroke]].<ref name="dcomplicationsnm1">Complications of leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016</ref> The median survival time of patients without treatment of neoplastic meningitis is 4-6 weeks.<ref name="prognosisnm123">Prognosis of neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 20, 2016</ref> | |||
==Diagnosis== | ==Diagnosis== | ||
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===History and Symptoms=== | ===History and Symptoms=== | ||
When evaluating a patient for neoplastic meningitis, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus when obtaining the history include review of common associated conditions such as [[intracerebral metastases]] and the distant primary tumors. Neoplastic meningitis should be suspected if there are simultaneous occurrence of symptoms or signs in more than one area of the [[neuraxis]].<ref>{{cite journal|title=Infiltration of the Leptomeninges by Systemic Cancer-A Clinical and Pathologic Study|doi=10.1001/archneur.1974.00490320010002.}}</ref> Symptoms of neoplastic meningitis include [[headaches]], [[confusion]], [[memory loss]], [[seizures]], [[diplopia|double vision]], [[hearing loss]], [[paresthesia]] and [[pain]] in the neck and back, and limb weakness.<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
* When evaluating a patient for neoplastic meningitis, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. | |||
* Other specific areas of focus when obtaining the history include review of common associated conditions such as [[intracerebral metastases]] and the distant primary tumors. Neoplastic meningitis should be suspected if there are simultaneous occurrence of symptoms or signs in more than one area of the [[neuraxis]].<ref>{{cite journal|title=Infiltration of the Leptomeninges by Systemic Cancer-A Clinical and Pathologic Study|doi=10.1001/archneur.1974.00490320010002.}}</ref> | |||
* Symptoms of neoplastic meningitis include [[headaches]], [[confusion]], [[memory loss]], [[seizures]], [[diplopia|double vision]], [[hearing loss]], [[paresthesia]] and [[pain]] in the neck and back, and limb weakness.<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
===Physical Examination=== | ===Physical Examination=== | ||
Common physical examination findings of neoplastic meningitis include [[altered mental status]], [[dementia]], [[hemiparesis]], [[ptosis]], [[nuchal rigidity]], bowel and bladder dysfunction, and [[papilledema]].<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
* Common physical examination findings of neoplastic meningitis include [[altered mental status]], [[dementia]], [[hemiparesis]], [[ptosis]], [[nuchal rigidity]], bowel and bladder dysfunction, and [[papilledema]].<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Laboratory findings consistent with the diagnosis of neoplastic meningitis include abnormal CSF analysis (increased opening pressure, increased leukocytes, elevated protein, decreased glucose, and positive tumor markers). Only 50% of those suspected with neoplastic meningitis are actually diagnosed and only the '''presence of malignant cells in the CSF''' is diagnostic.<ref name=dxnm123>Diagnosis of neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 20, 2016</ref> | |||
* Laboratory findings consistent with the diagnosis of neoplastic meningitis include abnormal CSF analysis (increased opening pressure, increased leukocytes, elevated protein, decreased glucose, and positive tumor markers). Only 50% of those suspected with neoplastic meningitis are actually diagnosed and only the '''presence of malignant cells in the CSF''' is diagnostic.<ref name="dxnm123">Diagnosis of neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 20, 2016</ref> | |||
===CT=== | ===CT=== | ||
There are no CT scan findings associated with neoplastic meningitis.<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
* There are no CT scan findings associated with neoplastic meningitis.<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
===MRI=== | ===MRI=== | ||
* On MRI, neoplastic meningitis is characterized by normal T1- and T2-weighted images. On contrast administration, there may be leptomeningeal enhancement scattered over the brain in a 'sugar coated' manner, which is fairly diagnostic for neoplastic meningitis.<ref name="eaturesradiographicfneomeningitis1">Radiographic features of leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 19, 2016</ref> | |||
===Other Imaging Findings=== | ===Other Imaging Findings=== | ||
* There are no other imaging findings associated with neoplastic meningitis.<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
===Other Diagnostic Studies=== | ===Other Diagnostic Studies=== | ||
* Other diagnostic studies for neoplastic meningitis include [[biopsy|meningeal biopsy]], which may be diagnostic if there are no systemic manifestations and the CSF analysis remain inconclusive.<ref name="AhnLim2013">{{cite journal|last1=Ahn|first1=Shin|last2=Lim|first2=Kyung Soo|title=Three Cases of Neoplastic Meningitis Initially Diagnosed with Infectious Meningitis in Emergency Department|journal=Case Reports in Emergency Medicine|volume=2013|year=2013|pages=1–4|issn=2090-648X|doi=10.1155/2013/561475}}</ref> | |||
==Treatment== | ==Treatment== | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
The mainstay of therapy for neoplastic meningitis is [[intrathecal chemotherapy]].<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> [[Radiotherapy]] may be used in patients with neoplastic meningitis for palliation of symptoms, reduce the bulky tumors, and correction of cerebrospinal fluid flow abnormalities.<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> Supportive care should be directed towards all patients with neoplastic meningitis, regardless of the treatment regimen ([[anticonvulsants]], [[corticosteroids]], and [[opiates]]).<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
===Surgery=== | ===Surgery=== | ||
[[Surgery]] is not the first-line treatment option for patients with neoplastic meningitis. Surgery is usually reserved for patients who need an intraventricular catheter placement for administration of cytotoxic drugs or placement of a ventriculoperitoneal shunt in patients with [[hydrocephalus|symptomatic hydrocephalus]].<ref name="Chamberlain2008">{{cite journal|last1=Chamberlain|first1=M. C.|title=Neoplastic Meningitis|journal=The Oncologist|volume=13|issue=9|year=2008|pages=967–977|issn=1083-7159|doi=10.1634/theoncologist.2008-0138}}</ref> | |||
===Prevention=== | ===Prevention=== | ||
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Latest revision as of 23:45, 13 August 2019
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Neoplastic meningitis Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Neoplastic meningitis overview On the Web |
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American Roentgen Ray Society Images of Neoplastic meningitis overview |
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Risk calculators and risk factors for Neoplastic meningitis overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]
Overview
Neoplastic meningitis is the development of meningitis due to infiltration of the subarachnoid space by tumor cells. Neoplastic meningitis was first reported in the 1870's.[1] Neoplastic meningitis refers to the spread of malignant cells through the cerebrospinal fluid space. These cells can be originated both in primary CNS tumors (e.g. drop-metastases), as well as from distant tumors that have metastasized (hematogenous spread).[2] The microscopic pathology of neoplastic meningitis may vary according to the primary cancer involved. Generally, on microscopic histopathological analysis, neoplastic meningitis is characterized by large, hyperchromatic cells.[3] Common causes of neoplastic meningitis include primary intracerebral malignancies (glioblastoma multiforme, anaplastic astrocytoma, medulloblastoma) and metastatic disease (breast cancer, lung cancer, melanoma, lymphoma, leukemia).[4] Neoplastic meningitis must be differentiated from infections (meningitis, Lyme disease, neurocysticercosis), neoplastic (intracerebral metastasis, dural metastasis), inflammatory (rheumatoid arthritis, multiple sclerosis, polychondritis), and granulomatous disorders (sarcoidosis, histiocytosis, Wegener's granulomatosis, vasculitis).[5] Neoplastic meningitis occurs in approximately 3-5% of patients with solid tumor, 5-15% of patients with leukemia, and 1-2% of patients with primary brain tumors.[6][7] Neoplastic meningitis has a widely disseminated and progressive presentation. If left untreated, neoplastic meningitis may progress to develop seizures, hydrocephalus, encephalopathy, and ultimately death.[8] Complications of neoplastic meningitis include hydrocephalus, encephalopathy, empyema, cerebritis, cerebral abscess, and stroke.[8] The median survival time of patients without treatment of neoplastic meningitis is 4-6 weeks.[9] Neoplastic meningitis should be suspected if there are simultaneous occurrence of symptoms or signs in more than one area of the neuraxis.[10] Symptoms of neoplastic meningitis include headaches, confusion, memory loss, seizures, double vision, hearing loss, paresthesia and pain in the neck and back, and limb weakness.[11] Common physical examination findings of neoplastic meningitis include altered mental status, dementia, hemiparesis, ptosis, nuchal rigidity, bowel and bladder dysfunction, and papilledema.[11] Laboratory findings consistent with the diagnosis of neoplastic meningitis include abnormal CSF analysis (increased opening pressure, increased leukocytes, elevated protein, decreased glucose, and positive tumor markers). Only 50% of those suspected with neoplastic meningitis are actually diagnosed and only the presence of malignant cells in the CSF is diagnostic.[12] Brain MRI is helpful in the diagnosis of neoplastic meningitis. On MRI, neoplastic meningitis is characterized by normal T1- and T2-weighted images. On contrast administration, there may be leptomeningeal enhancement scattered over the brain in a 'sugar coated' manner, which is fairly diagnostic for neoplastic meningitis.[13] Other diagnostic studies for neoplastic meningitis include meningeal biopsy, which may be diagnostic if there are no systemic manifestations and the CSF analysis remain inconclusive.[14] The mainstay of therapy for neoplastic meningitis is intrathecal chemotherapy.[11] Radiotherapy may be used in patients with neoplastic meningitis for palliation of symptoms, reduce the bulky tumors, and correction of cerebrospinal fluid flow abnormalities.[11] Supportive care should be directed towards all patients with neoplastic meningitis, regardless of the treatment regimen (anticonvulsants, corticosteroids, and opiates).[11] Surgery is not the first-line treatment option for patients with neoplastic meningitis. Surgery is usually reserved for patients who need an intraventricular catheter placement for administration of cytotoxic drugs or placement of a ventriculoperitoneal shunt in patients with symptomatic hydrocephalus.[11]
Historical Perspective
- The first case of neoplastic meningitis was described by Eberth in the 1870s.
Classification
There is no classification system established for neoplastic meningitis.
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).
- Cancer from a distant source enter the CSF by means of the following:[3]
- 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.
- 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.
- 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.
- 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.[5]
- Iatrogenic - from surgical procedures involving removal of a primary brain tumor
- Primary neoplastic meningitis has also been documented particularly with melanoma.[15]
Causes
- Common causes of neoplastic meningitis include primary intracerebral malignancies (glioblastoma multiforme, anaplastic astrocytoma, medulloblastoma) and metastatic disease (breast cancer, lung cancer, melanoma, lymphoma, leukemia).[4]
Differentiating Neoplastic Meningitis from other Diseases
- Neoplastic meningitis must be differentiated from infections (meningitis, Lyme disease, neurocysticercosis), neoplastic (intracerebral metastasis, dural metastasis), inflammatory (rheumatoid arthritis, multiple sclerosis, polychondritis), and granulomatous disorders (sarcoidosis, histiocytosis, Wegener's granulomatosis, vasculitis).[5]
Epidemiology and Demographics
- Neoplastic meningitis occurs in approximately 3-5% of patients with solid tumor, 5-15% of patients with leukemia, and 1-2% of patients with primary brain tumors.[6][7]
Risk Factors
- Factors that have been known to increase the risk of neoplastic meningitis involves:[4]
- Brain metastasis is one of the more obvious risk factors for neoplastic meningitis. Coexisting brain metastasis are associated with neoplastic meningitis in breast cancer (33-54%), lung cancer (56-82%) and melanoma (87-96%).
- Primary brain cancer always poses a risk for the development of neoplastic meningitis. It is diagnosed in 1-2% of cases of ependymoma, medulloblastoma, germinoma and glioblastoma combined.
- Brain surgery increases the chance of developing neoplastic meningitis. It has been observed after resection of brain tumor (particularly piecemeal resection vs en-block resection) particularly tumors located in the cerebellum. Other cranial surgeries done with involvement of ventricular system manipulation in a patient with known brain metastasis increases the risk. Furthermore, the incidence of neoplastic meningitis seem higher in patient treated with surgery followed by stereotactic radiosurgery compared with radiosurgery alone.
- ER-, PR-positivity in beast cancer increases incidence of neoplastic meningitis. Triple negative breast cancer and the HER2/neu gene positivity displays tropism for CNS metastasis. Among the histologic subtypes of breast cancer, loblular carcinoma demonstrated the highest prevalence for neoplastic meningitis.
Screening
- There is insufficient evidence to recommend routine screening for neoplastic meningitis.[16]
Natural History, Complications and Prognosis
- Neoplastic meningitis has a widely disseminated and progressive presentation. If left untreated, neoplastic meningitis may progress to develop seizures, hydrocephalus, encephalopathy, and ultimately death.[8]
- Complications of neoplastic meningitis include hydrocephalus, encephalopathy, empyema, cerebritis, cerebral abscess, and stroke.[8] The median survival time of patients without treatment of neoplastic meningitis is 4-6 weeks.[9]
Diagnosis
Staging
There is no established system for the staging of choroid plexus papilloma.[17]
History and Symptoms
- When evaluating a patient for neoplastic meningitis, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review.
- Other specific areas of focus when obtaining the history include review of common associated conditions such as intracerebral metastases and the distant primary tumors. Neoplastic meningitis should be suspected if there are simultaneous occurrence of symptoms or signs in more than one area of the neuraxis.[18]
- Symptoms of neoplastic meningitis include headaches, confusion, memory loss, seizures, double vision, hearing loss, paresthesia and pain in the neck and back, and limb weakness.[11]
Physical Examination
- Common physical examination findings of neoplastic meningitis include altered mental status, dementia, hemiparesis, ptosis, nuchal rigidity, bowel and bladder dysfunction, and papilledema.[11]
Laboratory Findings
- Laboratory findings consistent with the diagnosis of neoplastic meningitis include abnormal CSF analysis (increased opening pressure, increased leukocytes, elevated protein, decreased glucose, and positive tumor markers). Only 50% of those suspected with neoplastic meningitis are actually diagnosed and only the presence of malignant cells in the CSF is diagnostic.[12]
CT
- There are no CT scan findings associated with neoplastic meningitis.[11]
MRI
- On MRI, neoplastic meningitis is characterized by normal T1- and T2-weighted images. On contrast administration, there may be leptomeningeal enhancement scattered over the brain in a 'sugar coated' manner, which is fairly diagnostic for neoplastic meningitis.[13]
Other Imaging Findings
- There are no other imaging findings associated with neoplastic meningitis.[11]
Other Diagnostic Studies
- Other diagnostic studies for neoplastic meningitis include meningeal biopsy, which may be diagnostic if there are no systemic manifestations and the CSF analysis remain inconclusive.[14]
Treatment
Medical Therapy
The mainstay of therapy for neoplastic meningitis is intrathecal chemotherapy.[11] Radiotherapy may be used in patients with neoplastic meningitis for palliation of symptoms, reduce the bulky tumors, and correction of cerebrospinal fluid flow abnormalities.[11] Supportive care should be directed towards all patients with neoplastic meningitis, regardless of the treatment regimen (anticonvulsants, corticosteroids, and opiates).[11]
Surgery
Surgery is not the first-line treatment option for patients with neoplastic meningitis. Surgery is usually reserved for patients who need an intraventricular catheter placement for administration of cytotoxic drugs or placement of a ventriculoperitoneal shunt in patients with symptomatic hydrocephalus.[11]
Prevention
There are no primary or secondary preventive measures available for neoplastic meningitis.
References
- ↑ Neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 19, 2016
- ↑ Leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 20, 2016
- ↑ Berzero, Giulia; Diamanti, Luca; Di Stefano, Anna Luisa; Bini, Paola; Franciotta, Diego; Imarisio, Ilaria; Pedrazzoli, Paolo; Magrassi, Lorenzo; Morbini, Patrizia; Farina, Lisa Maria; Bastianello, Stefano; Ceroni, Mauro; Marchioni, Enrico (2015). "Meningeal Melanomatosis: A Challenge for Timely Diagnosis". BioMed Research International. 2015: 1–6. doi:10.1155/2015/948497. ISSN 2314-6133.
- ↑ 4.0 4.1 Pathology of leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 19, 2016
- ↑ 5.0 5.1 Leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016
- ↑ 6.0 6.1 Gleissner, Beate; Chamberlain, Marc Charles (2006). "Neoplastic meningitis". The Lancet Neurology. 5 (5): 443–452. doi:10.1016/S1474-4422(06)70443-4. ISSN 1474-4422.
- ↑ 7.0 7.1 Hayat, M. A. Brain metastases from primary tumors : epidemiology, biology, and therapy. London: Elsevier/Academic Press, 2014. Print.| url=https://books.google.com/books?id=IloXAwAAQBAJ&pg=PA43&lpg=PA43&dq=leptomeningeal+carcinomatosis+is+present+in+1-5%25+of+patients+with+solid+tumors,+5-15%25+of+patients+with+leukemia,+and+1-2%25+of+patients+with+primary+brain+tumors.&source=bl&ots=ehEaDBCT5f&sig=vvSxdxDjNMBe0CdCP6fEcMaYJqU&hl=en&sa=X&ved=0ahUKEwi2ueuw37bKAhUG8j4KHWUUCoIQ6AEILTAC#v=onepage&q=leptomeningeal%20carcinomatosis%20is%20present%20in%201-5%25%20of%20patients%20with%20solid%20tumors%2C%205-15%25%20of%20patients%20with%20leukemia%2C%20and%201-2%25%20of%20patients%20with%20primary%20brain%20tumors.&f=false. Accessed on January 19, 2016
- ↑ 8.0 8.1 8.2 8.3 Complications of leptomeningitis. Dr Amir Rezaee and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningitis. Accessed on January 21, 2016
- ↑ 9.0 9.1 Prognosis of neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 20, 2016
- ↑ "Infiltration of the Leptomeninges by Systemic Cancer-A Clinical and Pathologic Study". doi:10.1001/archneur.1974.00490320010002. Check
|doi=value (help). - ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 11.12 11.13 Chamberlain, M. C. (2008). "Neoplastic Meningitis". The Oncologist. 13 (9): 967–977. doi:10.1634/theoncologist.2008-0138. ISSN 1083-7159.
- ↑ 12.0 12.1 Diagnosis of neoplastic meningitis. Wikipedia 2016. https://en.wikipedia.org/wiki/Neoplastic_meningitis. Accessed on January 20, 2016
- ↑ 13.0 13.1 Radiographic features of leptomeningeal metastases. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/leptomeningeal-metastases. Accessed on January 19, 2016
- ↑ 14.0 14.1 Ahn, Shin; Lim, Kyung Soo (2013). "Three Cases of Neoplastic Meningitis Initially Diagnosed with Infectious Meningitis in Emergency Department". Case Reports in Emergency Medicine. 2013: 1–4. doi:10.1155/2013/561475. ISSN 2090-648X.
- ↑ "Neoplastic Meningitis due to Lung, Breast and Melanoma Metastases" (PDF).
- ↑ Early detection, diagnosis, and staging of brain tumors. American cancer society. http://www.cancer.org/cancer/braincnstumorsinadults/detailedguide/brain-and-spinal-cord-tumors-in-adults-detection
- ↑ Chandana SR, Movva S, Arora M, Singh T (2008). "Primary brain tumors in adults". Am Fam Physician. 77 (10): 1423–30. PMID 18533376.
- ↑ "Infiltration of the Leptomeninges by Systemic Cancer-A Clinical and Pathologic Study". doi:10.1001/archneur.1974.00490320010002. Check
|doi=value (help).