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Current Neurology and Neuroscience Reports

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01-12-2013 | Neuro-Ophthalmology (A Kawasaki, Section Editor)

Neuro-ophthalmologic Complications of Neoplastic Leptomeningeal Disease

Author: Gabriella Szatmáry

Published in: Current Neurology and Neuroscience Reports | Issue 12/2013

Abstract

Neoplastic leptomeningeal disease (NLD), which encompasses both primary and secondary leptomeningeal tumors, has a devastating impact on the life of cancer patients. The present diagnostic technical armamentarium is insufficient for early diagnosis of NLD. However, NLD may present with subtle neuro-ophthalmic features at a time of relatively small tumor burden, which gives the provider first encountering these patients the window of opportunity for early diagnosis and consequently improved life expectancy and quality of life of these patients. Therefore, familiarity with early, often subtle neuro-ophthalmic features is an essential tool for diagnosing these patients prior to the development of fixed deficits, which usually portend a dismal prognosis. Future evolving laboratory and neuroimaging technologies are expected to advance our understanding of underlying pathophysiology and early detection of NLD. This paper provides an up-to-date review and synthesis of the current literature with focus on neuro-ophthalmic features and their underlying pathophysiology.

•• Clarke JL. Leptomeningeal metastasis from systemic cancer. Continuum. 2012;18:328–42. This review article of leptomeningeal metastasis from systemic cancer is an in-depth recap of LM and includes clinical presentation, diagnostic evaluation, and therapy. It is notable for its clinically oriented style with representative case presentations. PubMed

• Noval S, Ortiz-Pérez S, Sánchez-Dalmau BF, et al. Neuro-ophthalmological features of primary diffuse leptomeningeal gliomatosis. J Neuroophthalmol. 2011;31:299–305. In this article the authors present 2 new cases and review the literature on the neuro-ophthalmic features of primary diffuse leptomeningeal gliomatosis, a rare primary neoplasm of the leptomeninges. PubMedCrossRef

Lachance DH, O'Neill BP, Macdonald DR, et al. Primary leptomeningeal lymphoma: report of 9 cases, diagnosis with immunocytochemical analysis, and review of the literature. Neurology. 1991;41:95–100.PubMedCrossRef

Demir MK, Aker FV, Akinci O, Ozgültekin A. Case 134: primary leptomeningeal melanomatosis. Radiology. 2008;247:905–9.PubMedCrossRef

Zadro I, Brinar VV, Barun B, et al. Primary diffuse meningeal melanomatosis. Neurologist. 2010;16:117–9.PubMedCrossRef

Bernardini FP, Croxatto JO, Nozza P, Rossi A, Capris P. Primary diffuse leptomeningeal gliomatosis in children: a clinical pathologic correlation. Ophthal Plast Reconstr Surg. 2013;29:93–7.PubMedCrossRef

Scott BJ, Kesari S. Leptomeningeal metastases in breast cancer. Am J Cancer Res. 2013;3:117–26.PubMed

Le Rhun E, Taillibert S, Zairi F, et al. A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer. J Neurooncol. 2013;113:83–92.PubMedCrossRef

Niwińska A, Rudnicka H, Murawska M. Breast cancer leptomeningeal metastasis: propensity of breast cancer subtypes for leptomeninges and the analysis of factors influencing survival. Med Oncol. 2013;30:408.PubMedCrossRef

10.

Pape E, Desmedt E, Zairi F, et al. Leptomeningeal metastasis in melanoma: a prospective clinical study of nine patients. In Vivo. 2012;26:1079–86.PubMed

11.

Harstad L, Hess KR, Groves MD. Prognostic factors and outcomes in patients with leptomeningeal melanomatosis. Neuro Oncol. 2008;10:1010–8.PubMedCrossRef

12.

Schaefer N, Rasch K, Moehlenbruch M, et al. Leptomeningeal melanomatosis: stabilization of disease due to radiation, temozolomide and intrathecal liposomal cytarabine. Acta Oncol. 2011;50:1260–2.PubMedCrossRef

13.

Morris PG, Reiner AS, Szenberg OR, Clarke JL, et al. Leptomeningeal metastasis from nonsmall cell lung cancer: survival and the impact of whole brain radiotherapy. J Thorac Oncol. 2012;7:382–5.PubMedCrossRef

14.

Nagpal S, Riess J, Wakelee H. Treatment of leptomeningeal spread of NSCLC: a continuing challenge. Curr Treat Options Oncol. 2012;13:491–504.PubMedCrossRef

15.

Sabater AL, Sadaba LM, de Nova E. Ocular symptoms secondary to meningeal carcinomatosis in a patient with lung adenocarcinoma: a case report. BMC Ophthalmol. 2012;12:65.

16.

Kleinfeld K, Peters WH, Stephenson C, Azar NJ. Leptomeningeal metastasis from occult signet-ring cell colon adenocarcinoma presenting with isolated headache. J Clin Neurosci. 2013;20:890–2.PubMedCrossRef

17.

Tomita H, Yasui H, Boku N, et al. Leptomeningeal carcinomatosis associated with gastric cancer. Int J Clin Oncol. 2012;17:361–6.PubMedCrossRef

18.

•• Le Rhun E, Taillibert S, Chamberlain MC. Carcinomatous meningitis: Leptomeningeal metastases in solid tumors. Surg Neurol Int. 2013;4 Suppl 4:S265–88. This is a comprehensive review of patients with systemic solid tumors with leptomeningeal metastasis with a focus on neurosurgically relevant issues. The strength of this paper is the detailed description of available and investigational treatments and treatment-related complications. PubMed

19.

Gleissner B, Chamberlain MC. Neoplastic meningitis. Lancet Neurol. 2006;5:443–52.PubMedCrossRef

20.

Yeung SN, Paton KE, Dorovini-Zis K, Chew JB, White VA. Histopathologic features of multiple myeloma involving the optic nerves. J Neuroophthalmol. 2008;28:12–6.PubMedCrossRef

21.

Stojkovic T, de Seze J, Maurage CA, et al. Atypical form of non-Langerhans histiocytosis with disseminated brain and leptomeningeal lesions. J Neurol Neurosurg Psychiatry. 2000;69:675–8.PubMedCrossRef

22.

• Gold DR, Nadel RE, Vangelakos CG, et al. Pearls and oy-sters: the utility of cytology and flow cytometry in the diagnosis of leptomeningeal leukemia. Neurology. 2013;80:e156–9. This article is notable for its clinically relevant style presentation of a leukemia patient with leptomeningeal spread and its succinct diagnostic recommendations. PubMedCrossRef

23.

Liang H, Luo B, Liu J. Non-Hodgkin lymphoma presenting with ophthalmoplegia and gingival pain. J Neuroophthalmol. 2006;26:153–4.PubMedCrossRef

24.

Choi JY, Kafkala C, Foster CS. Primary intraocular lymphoma: a review. Semin Ophthalmol. 2006;21:125–33.PubMedCrossRef

25.

Kim SK, Chan CC, Wallace DJ. Management of primary intraocular lymphoma. Curr Oncol Rep. 2005;7:74–9.PubMedCrossRef

26.

Valluri S, Moorthy RS, Khan A, Rao NA. Combination treatment of intraocular lymphoma. Retina. 1995;15:125–9.PubMedCrossRef

27.

Pérez-Bovet J, Rimbau-Muñoz J, Martín-Ferrer S. Anaplastic ependymoma with holocordal and intracranial meningeal carcinomatosis and holospinal bone metastases. Neurosurgery. 2013;72:E497–503.PubMedCrossRef

28.

Aroichane M, Miller NR, Eggenberger ER. Glioblastoma multiforme masquerading as pseudotumor cerebri: a case report. J Clin Neuroophthalmol. 1993;13:105–12.PubMed

29.

Lawton CD, Nagasawa DT, Yang I, Fessler RG, Smith ZA. Leptomeningeal spinal metastases from glioblastoma multiforme: treatment and management of an uncommon manifestation of disease. J Neurosurg Spine. 2012;17:438–48.PubMedCrossRef

30.

Wei G, Kang X, Liu X, Yin H. Teaching neuro-images: an unusual cause of conus medullaris syndrome. Neurology. 2013;81:e30–1.PubMedCrossRef

31.

Mehta RI, Cutler AR, Lasky III JL, et al. "Primary" leptomeningeal medulloblastoma. Hum Pathol. 2009;40:1661–5.PubMedCrossRef

32.

Wu X, Northcott PA, Dubuc A, et al. Clonal selection drives genetic divergence of metastatic medulloblastoma. Nature. 2012;482:529–33.PubMedCrossRef

33.

Ahn JH, Lee SH, Kim S, et al. Risk for leptomeningeal seeding after resection for brain metastases: implication of tumor location with mode of resection. Neurosurgery. 2012;116(5):984–93.

34.

Rizzo JF. Embryology, anatomy, and physiology of the afferent visual pathway. In: Miller NR, Newman NJ, Biousse V, Kerrison JB, eds. Walsh & Hoyt's Clinical Neuro-Ophthalmology, 6th ed. Lippincott Williams & Wilkins; 2005: p. 33.

35.

Friedman D. Papilledema. In: Miller NR, Newman NJ, Biousse V, Kerrison JB, eds. Walsh & Hoyt's Clinical Neuro-Ophthalmology, 6th ed. Lippincott Williams & Wilkins, 2005: p. 267.

36.

Shanthaveerappa TR, Bourne GH. Arachnoid villi in the optic nerve of man and monkey. Exp Eye Res. 1964;3:31–5.PubMedCrossRef

37.

Jayatilaka AD. A note on arachnoid villi in relation to human optic nerves. J Anat. 1967;101(Pt 1):171–3.PubMed

38.

Bulat M, Klarica M. Recent insights into a new hydrodynamics of the cerebrospinal fluid. Brain Res Rev. 2011;65:99–112.PubMedCrossRef

39.

Killer HE, Jaggi GP, Miller NR, et al. Cerebrospinal fluid dynamics between the basal cisterns and the subarachnoid space of the optic nerve in patients with papilloedema. Br J Ophthalmol. 2011;95:822–7.PubMedCrossRef

40.

Killer HE, Jaggi GP, Miller NR. Optic nerve compartment syndrome. Acta Ophthalmol. 2011;89:e472.PubMedCrossRef

41.

Kokkoris CP. Leptomeningeal carcinomatosis. How does cancer reach the pia-arachnoid? Cancer. 1983;51:154–60.PubMedCrossRef

42.

Li K, Zhang G, Zhao J, Wang X, Li Y, Hu Y. Vascular endothelial growth factor antisense oligonucleotides inhibit leptomeningeal metastasis in vivo. Med Oncol. 2011;28:1116–22.PubMedCrossRef

43.

Katz JL, Valsamis MP, Jampel RS. Ocular signs in diffuse carcinomatous meningitis. AJOPHT. 1961;52:681–90.

44.

McFadzean R, Brosnahan D, Doyle D, et al. A diagnostic quartet in leptomeningeal infiltration of the optic nerve sheath. J Neuroophthalmol. 1994;14:175–82.PubMedCrossRef

45.

• Ibrahim M, Parmar H, Gandhi D, Mukherji SK. Imaging nuances of perineural spread of head and neck malignancies. J Neuroophthalmol. 2007;27:129–37. This paper is a comprehensive and neuro-ophthalmologically focused neuroimaging review of head and neck cancer patients with secondary perineural spread to central nervous system. PubMedCrossRef

46.

Dunn M, Morgan MB. Perineural invasion progressing to leptomeningeal carcinomatosis: is the absence of peripheral nerves an important sign? J Am Acad Dermatol. 2010;62:270–6.PubMedCrossRef

47.

Trobe JD, Hood CI, Parsons JT, Quisling RG. Intracranial spread of squamous carcinoma along the trigeminal nerve. Arch Ophthalmol. 1982;100:608–11.PubMedCrossRef

48.

Hayat G, Ehsan T, Selhorst JB, Manepali A. Magnetic resonance evidence of perineural metastasis. J Neuroimaging. 1995;5:122–5.PubMed

49.

Coupland SE, Damato B. Understanding intraocular lymphomas. Clin Exp Ophthalmol. 2008;36:564–78.CrossRef

50.

Matsuoka M, Yoshida H, Kinoshita Y, Nishimura T. Two cases of intraocular lymphoma diagnosed by analyses of vitreous and infusion fluid. Clin Ophthalmol. 2013;7:691–4.PubMedCrossRef

51.

Cooper IS, Kernohan JW. Heterotopic glial nests in subarachnoid space: histopathologic characteristics, mode of origin and relation to meningeal gliomas. J Neuropathol Exp Neurol. 1951;10:16–29.PubMed

52.

Dimou J, Tsui A, Maartens NF, King JA. Primary diffuse leptomeningeal gliosarcomatosis with a sphenoid/sellar mass: confirmation of the ectopic glial tissue theory? J Clin Neurosci. 2011;18:702–4.PubMedCrossRef

53.

McCrary III JA, Patrinely JR, Font RL. Progressive blindness caused by metastatic occult signet-ring cell gastric carcinoma. Arch Ophthalmol. 1986;104:410–3.PubMedCrossRef

54.

Teare JP, Whitehead M, Rake MO, Coker RJ. Rapid onset of blindness due to meningeal carcinomatosis from an oesophageal adenocarcinoma. Postgrad Med J. 1991;67:909–11.PubMedCrossRef

55.

Susac JO, Smith JL, Powell JO. Carcinomatous optic neuropathy. Am J Ophthalmol. 1973;76:672–9.PubMed

56.

Schaible ER, Golnik KC. Combined obstruction of the central retinal artery and vein associated with meningeal carcinomatosis. Arch Ophthalmol. 1993;111:1467–8.PubMedCrossRef

57.

Clarke JL, Perez HR, Jacks LM, Panageas KS, Deangelis LM. Leptomeningeal metastases in the MRI era. Neurology. 2010;74:1449–54.PubMedCrossRef

58.

Fukui MB, Meltzer CC, Kanal E, Smirniotopoulos JG. MR imaging of the meninges. II. Neoplastic disease. Radiology. 1996;201:605–12.PubMed

59.

Sze G, Soletsky S, Bronen R, Krol G. MR imaging of the cranial meninges with emphasis on contrast enhancement and meningeal carcinomatosis. Am J Neuroradiol. 1989;10:965–75.PubMed

60.

Hiraka T, Koyama S, Kurokawa K, et al. Reversible distension of the subarachnoid space around the optic nerves in a case of idiopathic hypertrophic pachymeningitis. Magn Reson Med Sci. 2012;11:141–4.PubMedCrossRef

61.

Chamberlain MC, Kormanik PA. Prognostic significance of 111indium-DTPA CSF flow studies in leptomeningeal metastases. Neurology. 1996;46:1674–7.PubMedCrossRef

62.

Pauls S, Fischer AC, Brambs HJ, et al. Use of magnetic resonance imaging to detect neoplastic meningitis: limited use in leukemia and lymphoma but convincing results in solid tumors. Eur J Radiol. 2012;81:974–8.PubMedCrossRef

63.

Ahn S, Lim KS. Three cases of neoplastic meningitis initially diagnosed with infectious meningitis in emergency department. Case Rep Emerg Med. 2013;2013:561475.PubMed

64.

Shiraishi Y, Kimura A, Seichi A, et al. Multifocal extramedullary spinal sarcoid lesions mimicking leptomeningeal metastasis. J Orthop Sci. 2013;18:343–6.PubMedCrossRef

65.

Frohman LP, Guirgis M, Turbin RE, Bielory L. Sarcoidosis of the anterior visual pathway: 24 new cases. J Neuroophthalmol. 2003;23:190–7.PubMedCrossRef

66.

Rucker JC, Biousse V, Newman NJ. Leptomeningeal enhancement and venous abnormalities in granulomatous angiitis of the central nervous system. J Neuroophthalmol. 2003;23:148–50.PubMedCrossRef

67.

Allmendinger AM, Viswanadhan N, Klufas RA, Hsu L. Diffuse cauda equina enhancement in a middle aged male with Susac syndrome and symptomatic cauda equina syndrome. J Neurol Sci. 2013;333(1–2):25–8.

68.

Nicastro N, Schnider A, Leemann B. Anaplastic medullary ependymoma presenting as subarachnoid hemorrhage. Case Rep Neurol Med. 2013;2013:701820. doi:10.1155/2013/701820.

69.

Schumacher DJ, Tien RD, Friedman H. Gadolinium enhancement of the leptomeninges caused by hydrocephalus: a potential mimic of leptomeningeal metastasis. Am J Neuroradiol. 1994;15:639–41.PubMed

70.

Milburn-McNulty P, Michael B, Moxham N, Fletcher N, Crooks D. How to do it: how to get the most out of cerebrospinal fluid cytology. Pract Neurol. 2012;12:241–3.PubMedCrossRef

71.

Ren S, Huang Y, Shah P, Manucha V. Metastatic squamous cell carcinoma in cerebrospinal fluid: why a rare diagnosis on cytology? Acta Cytol. 2012;56:209–13.PubMedCrossRef

72.

Nayak L, Fleisher M, Gonzalez-Espinoza R, et al. Rare cell capture technology for the diagnosis of leptomeningeal metastasis in solid tumors. Neurology. 2013;80:1598–605.PubMedCrossRef

73.

Le Rhun E, Tu Q, De Carvalho Bittencourt M, et al. Detection and quantification of CSF malignant cells by the CellSearch technology in patients with melanoma leptomeningeal metastasis. Med Oncol. 2013;30:538.PubMedCrossRef

74.

Bougel S, Lhermitte B, Gallagher G, et al. Methylation of the hTERT promoter: a novel cancer biomarker for leptomeningeal metastasis detection in cerebrospinal fluids. Clin Cancer Res. 2013;19:2216–23.PubMedCrossRef

75.

Walbert T, Groves MD. Known and emerging biomarkers of leptomeningeal metastasis and its response to treatment. Future Oncol. 2010;6:287–97.PubMedCrossRef

76.

Reijneveld JC, Brandsma D, Boogerd W, et al. CSF levels of angiogenesis-related proteins in patients with leptomeningeal metastases. Neurology. 2005;65:1120–2.PubMedCrossRef

77.

van de Langerijt B, Gijtenbeek JM, de Reus HP, et al. CSF levels of growth factors and plasminogen activators in leptomeningeal metastases. Neurology. 2006;67:114–9.PubMedCrossRef

78.

Hayashi Y, Kato T, Tanaka Y, et al. Markedly ring-enhanced optic nerves due to metastasis of signet-ring cell gastric carcinoma. Intern Med. 2010;49:517.PubMedCrossRef

79.

Wolfe GI, Galetta SK, Mollman JE. Spontaneous remission of papilledema and sixth nerve palsy in acute lymphoblastic leukemia. J Neuroophthalmol. 1994;14:91–4.PubMedCrossRef

80.

Bruggers CS, Friedman HS, Phillips PC, et al. Leptomeningeal dissemination of optic pathway gliomas in three children. Am J Ophthalmol. 1991;111(6):719–23.

81.

Wabbels B, Demmler A, Seitz J, et al. Unilateral adult malignant optic nerve glioma. Graefes Arch Clin Exp Ophthalmol. 2004;242:741–8.PubMedCrossRef

82.

Delgado-Alvarado M, Gómez-Román J, Sánchez-Salmón E, et al. Nonanaplastic pleomorphic xanthoastrocytoma with meningeal dissemination presenting with bilateral visual loss. J Neuroimaging. 2013. doi:10.1111/jon.12031.

83.

Kim YH, Kim JW, Park CK, et al. Papillary tumor of pineal region presenting with leptomeningeal seeding. Neuropathology. 2010;30:654–60.PubMedCrossRef

84.

Kobayashi M, Hara K, Nakatsukasa M, et al. Primary spinal leptomeningeal gliomatosis presenting visual disturbance as the initial symptom: case report. Acta Neurochir. 1996;138:480–1.PubMedCrossRef

85.

Manusow JS, Lee-Wing M, Rahman J, Mis A. Primary leptomeningeal lymphoma masquerading as pseudotumor cerebri. Can J Ophthalmol. 2009;44:e19–20.PubMedCrossRef

86.

Ahmed RM, King J, Gibson J, et al. Spinal leptomeningeal lymphoma presenting as pseudotumor syndrome. J Neuroophthalmol. 2013;33:13–6.PubMedCrossRef

87.

Oechsle K, Lange-Brock V, Kruell A, et al. Prognostic factors and treatment options in patients with leptomeningeal metastases of different primary tumors: a retrospective analysis. J Cancer Res Clin Oncol. 2010;136:1729–35.PubMedCrossRef

88.

Chamberlain MC, Johnston SK, Glantz MJ. Neoplastic meningitis-related prognostic significance of the Karnofsky performance status. Arch Neurol. 2009;66:74–8.PubMedCrossRef

89.

Chamberlain MC, Johnston SK. Neoplastic meningitis: survival as a function of cerebrospinal fluid cytology. Cancer. 2009;115:1941–6.PubMedCrossRef

90.

Le Rhun E, Zairi F. Treatment of the leptomeningeal metastases related to solid tumors. Bull Cancer. 2013;100:765–74.PubMed

91.

Grewal J, Saria MG, Kesari SJ. Novel approaches to treating leptomeningeal metastases. Neurooncol. 2012;106:225–34.CrossRef

92.

Bot I, Blank CU, Brandsma D. Clinical and radiological response of leptomeningeal melanoma after whole brain radiotherapy and ipilimumab. J Neurol. 2012;259:1976–8.PubMedCrossRef

93.

Boogerd W, van den Bent MJ, Koehler PJ, et al. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomized study. Eur J Cancer. 2004;40:2726–33.PubMedCrossRef

94.

Park J, Zhang Y, Vykhodtseva N, Jolesz FA, McDannold NJ. The kinetics of blood brain barrier permeability and targeted doxorubicin delivery into brain induced by focused ultrasound. J Control Release. 2012;162:134–42.PubMedCrossRef

95.

Grewal J, Saria M, Grewal HK, Kesari S. Neoplastic meningitis resulting from hematological malignancies: pharmacokinetic considerations and maximizing outcome. Clin Investig. 2011;1:1391–402.CrossRef

96.

Chamberlain MC. Neurotoxicity of intra-CSF liposomal cytarabine (DepoCyt) administered for the treatment of leptomeningeal metastases: a retrospective case series. J Neurooncol. 2012;109:143–8.PubMedCrossRef

Title: Neuro-ophthalmologic Complications of Neoplastic Leptomeningeal Disease
Author: Gabriella Szatmáry
Publication date: 01-12-2013
Publisher: Springer US
Published in: Current Neurology and Neuroscience Reports / Issue 12/2013
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI: https://doi.org/10.1007/s11910-013-0404-x

At a glance: The STEP trials

Springer Medicine

Neuro-ophthalmologic Complications of Neoplastic Leptomeningeal Disease

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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