Skip to main content
Top
Published in: BMC Neurology 1/2016

Open Access 01-12-2016 | Research article

Clinical features, treatment and outcome in neurosarcoidosis: systematic review and meta-analysis

Authors: Daan Fritz, Diederik van de Beek, Matthijs C. Brouwer

Published in: BMC Neurology | Issue 1/2016

Login to get access

Abstract

Background

Neurosarcoidosis is a rare variant of sarcoidosis and is only described in small cohort studies. We define clinical features, treatment and outcome of patients with neurosarcoidosis over the last 35 years.

Methods

We performed a systematic review and meta-analysis of studies on neurosarcoidosis published between 1980 and 2016. Studies were included if they reported at least 5 cases. Studies describing one specific neurological presentation were excluded.

Results

We identified 29 articles describing 1088 patients diagnosed between 1965 and 2015. Neurosarcoidosis occurred in 5% of patients with systemic sarcoidosis. Mean age at presentation was 43 years and neurological symptoms were the first clinical manifestation of sarcoidosis in 52%. The most commonly reported feature of neurosarcoidosis was cranial neuropathy in 55%, with the facial and optic nerve most commonly affected, followed by headache in 32%. Pleiocytosis and elevated CSF protein were found in 58 and 63%. MRI of the brain showed abnormalities in 70%. Chest X-ray, chest CT, or gallium-67-scintigraphy showed findings consistent with sarcoidosis in 60%, 70% and 69%, respectively. First line therapy with corticosteroids was initiated in 434 of 539 patients (81%). Second and third line therapy was started in 27 and 9%. Outcome consisted of complete remission in 27%, incomplete remission in 32%, stable disease in 24%, deterioration in 6% and death in 5%.

Conclusion

Neurosarcoidosis has a heterogeneous clinical presentation and the diagnosis can be difficult because of low sensitivity of ancillary investigations. New treatments have emerged, but nevertheless one third of patients do not respond to treatment. Prospective cohort studies and RCTs on treatment are urgently needed.
Appendix
Available only for authorised users
Literature
4.
go back to reference Segal BM. Neurosarcoidosis: diagnostic approaches and therapeutic strategies. Curr Opin Neurol. 2013;26(3):307–13.CrossRefPubMed Segal BM. Neurosarcoidosis: diagnostic approaches and therapeutic strategies. Curr Opin Neurol. 2013;26(3):307–13.CrossRefPubMed
5.
go back to reference Hoitsma E, Faber CG, Drent M, Sharma OP. Neurosarcoidosis: a clinical dilemma. Lancet Neurol. 2004;3(7):397–407.CrossRefPubMed Hoitsma E, Faber CG, Drent M, Sharma OP. Neurosarcoidosis: a clinical dilemma. Lancet Neurol. 2004;3(7):397–407.CrossRefPubMed
6.
go back to reference Allen RK, Sellars RE, Sandstrom PA. A prospective study of 32 patients with neurosarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20(2):118–25.PubMed Allen RK, Sellars RE, Sandstrom PA. A prospective study of 32 patients with neurosarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2003;20(2):118–25.PubMed
7.
8.
go back to reference Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, Scadding JW, Thompson EJ, Chamoun V, Miller DH, et al. Central nervous system sarcoidosis-diagnosis and management. QJM. 1999;92(2):103–17.CrossRefPubMed Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, Scadding JW, Thompson EJ, Chamoun V, Miller DH, et al. Central nervous system sarcoidosis-diagnosis and management. QJM. 1999;92(2):103–17.CrossRefPubMed
9.
go back to reference Marangoni S, Argentiero V, Tavolato B. Neurosarcoidosis. Clinical description of 7 cases with a proposal for a new diagnostic strategy. J Neurol. 2006;253(4):488–95.CrossRefPubMed Marangoni S, Argentiero V, Tavolato B. Neurosarcoidosis. Clinical description of 7 cases with a proposal for a new diagnostic strategy. J Neurol. 2006;253(4):488–95.CrossRefPubMed
10.
go back to reference Tavee JO, Stern BJ. Neurosarcoidosis. Continuum. Neurol Systemic Dis. 2014;20(3):545–59. Tavee JO, Stern BJ. Neurosarcoidosis. Continuum. Neurol Systemic Dis. 2014;20(3):545–59.
11.
go back to reference Elkin R, Willcox PA. Neurosarcoidosis. A report of 5 cases. S Afr Med J. 1985;67(23):943–6.PubMed Elkin R, Willcox PA. Neurosarcoidosis. A report of 5 cases. S Afr Med J. 1985;67(23):943–6.PubMed
12.
go back to reference Pentland B, Mitchell JD, Cull RE, Ford MJ. Central nervous system sarcoidosis. Q J Med. 1985;56(220):457–65.PubMed Pentland B, Mitchell JD, Cull RE, Ford MJ. Central nervous system sarcoidosis. Q J Med. 1985;56(220):457–65.PubMed
13.
go back to reference Stern BJ, Krumholz A, Johns C, Scott P, Nissim J. Sarcoidosis and its neurological manifestations. Arch Neurol. 1985;42(9):909–17.CrossRefPubMed Stern BJ, Krumholz A, Johns C, Scott P, Nissim J. Sarcoidosis and its neurological manifestations. Arch Neurol. 1985;42(9):909–17.CrossRefPubMed
14.
go back to reference Oksanen V. Neurosarcoidosis: clinical presentations and course in 50 patients. Acta Neurol Scand. 1986;73(3):283–90.CrossRefPubMed Oksanen V. Neurosarcoidosis: clinical presentations and course in 50 patients. Acta Neurol Scand. 1986;73(3):283–90.CrossRefPubMed
15.
go back to reference Chen RC, McLeod JG. Neurological complications of sarcoidosis. Clin Exp Neurol. 1989;26:99–112.PubMed Chen RC, McLeod JG. Neurological complications of sarcoidosis. Clin Exp Neurol. 1989;26:99–112.PubMed
16.
go back to reference Chapelon C, Ziza JM, Piette JC, Levy Y, Raguin G, Wechsler B, Bitker MO, Bletry O, Laplane D, Bousser MG, et al. Neurosarcoidosis: signs, course and treatment in 35 confirmed cases. Medicine (Baltimore). 1990;69(5):261–76.CrossRef Chapelon C, Ziza JM, Piette JC, Levy Y, Raguin G, Wechsler B, Bitker MO, Bletry O, Laplane D, Bousser MG, et al. Neurosarcoidosis: signs, course and treatment in 35 confirmed cases. Medicine (Baltimore). 1990;69(5):261–76.CrossRef
17.
go back to reference Zouaoui A, Maillard JC, Dormont D, Chiras J, Marsault C. MRI in neurosarcoidosis. J Neuroradiol. 1992;19(4):271–84.PubMed Zouaoui A, Maillard JC, Dormont D, Chiras J, Marsault C. MRI in neurosarcoidosis. J Neuroradiol. 1992;19(4):271–84.PubMed
18.
go back to reference Radziwill A, Weder B. Neurosarcoidosis of the central nervous system. Analysis of the long-term follow-up of 8 cases. Nervenarzt. 1995;66(12):915–22.PubMed Radziwill A, Weder B. Neurosarcoidosis of the central nervous system. Analysis of the long-term follow-up of 8 cases. Nervenarzt. 1995;66(12):915–22.PubMed
19.
go back to reference Lower EE, Broderick JP, Brott TG, Baughman RP. Diagnosis and management of neurological sarcoidosis. Arch Intern Med. 1997;157(16):1864–8.CrossRefPubMed Lower EE, Broderick JP, Brott TG, Baughman RP. Diagnosis and management of neurological sarcoidosis. Arch Intern Med. 1997;157(16):1864–8.CrossRefPubMed
20.
go back to reference Sharma OP. Neurosarcoidosis: a personal perspective based on the study of 37 patients. Chest. 1997;112(1):220–8.CrossRefPubMed Sharma OP. Neurosarcoidosis: a personal perspective based on the study of 37 patients. Chest. 1997;112(1):220–8.CrossRefPubMed
21.
go back to reference Briner VA, Muller A, Gebbers JO. Neurosarcoidosis. Schweiz Med Wochenschr. 1998;128(21):799–810.PubMed Briner VA, Muller A, Gebbers JO. Neurosarcoidosis. Schweiz Med Wochenschr. 1998;128(21):799–810.PubMed
22.
go back to reference Pavese P, Brion JP, Chabre O, Fauconnier J, Pasquier B. Neurologic involvement in sarcoidosis. Federation of Systemic Diseases of Grenoble. Presse Med. 1999;28(4):168–72.PubMed Pavese P, Brion JP, Chabre O, Fauconnier J, Pasquier B. Neurologic involvement in sarcoidosis. Federation of Systemic Diseases of Grenoble. Presse Med. 1999;28(4):168–72.PubMed
23.
go back to reference Ferriby D, De Seze J, Stojkovic T, Hachulla E, Wallaert B, Destee A, Hatron PY, Vermersch P. Long-term follow-up of neurosarcoidosis. Neurology. 2001;57(5):927–9.CrossRefPubMed Ferriby D, De Seze J, Stojkovic T, Hachulla E, Wallaert B, Destee A, Hatron PY, Vermersch P. Long-term follow-up of neurosarcoidosis. Neurology. 2001;57(5):927–9.CrossRefPubMed
24.
go back to reference Heuser K, Kerty E. Neuro-ophthalmological findings in sarcoidosis. Acta Ophthalmol Scand. 2004;82(6):723–9.CrossRefPubMed Heuser K, Kerty E. Neuro-ophthalmological findings in sarcoidosis. Acta Ophthalmol Scand. 2004;82(6):723–9.CrossRefPubMed
25.
go back to reference Kellinghaus C, Schilling M, Ludemann P. Neurosarcoidosis: clinical experience and diagnostic pitfalls. Eur Neurol. 2004;51(2):84–8.CrossRefPubMed Kellinghaus C, Schilling M, Ludemann P. Neurosarcoidosis: clinical experience and diagnostic pitfalls. Eur Neurol. 2004;51(2):84–8.CrossRefPubMed
26.
go back to reference Karouache A, Mounach J, Aziz N, Bouraza A, Satte A, Ouhabi H, Rafiq R, Boutaleb N, Mossadaq R. A report of 9 cases of neurosarcoidosis. Rev Neurol. 2005;161(11):1091–101.CrossRefPubMed Karouache A, Mounach J, Aziz N, Bouraza A, Satte A, Ouhabi H, Rafiq R, Boutaleb N, Mossadaq R. A report of 9 cases of neurosarcoidosis. Rev Neurol. 2005;161(11):1091–101.CrossRefPubMed
27.
go back to reference Spencer TS, Campellone JV, Maldonado I, Huang N, Usmani Q, Reginato AJ. Clinical and magnetic resonance imaging manifestations of neurosarcoidosis. Semin Arthritis Rheum. 2005;34(4):649–61.CrossRefPubMed Spencer TS, Campellone JV, Maldonado I, Huang N, Usmani Q, Reginato AJ. Clinical and magnetic resonance imaging manifestations of neurosarcoidosis. Semin Arthritis Rheum. 2005;34(4):649–61.CrossRefPubMed
28.
go back to reference Joseph FG, Scolding NJ. Neurosarcoidosis: a study of 30 new cases. J Neurol Neurosurg Psychiatry. 2009;80(3):297–304.CrossRefPubMed Joseph FG, Scolding NJ. Neurosarcoidosis: a study of 30 new cases. J Neurol Neurosurg Psychiatry. 2009;80(3):297–304.CrossRefPubMed
29.
go back to reference Pawate S, Moses H, Sriram S. Presentations and outcomes of neurosarcoidosis: a study of 54 cases. QJM. 2009;102(7):449–60.CrossRefPubMed Pawate S, Moses H, Sriram S. Presentations and outcomes of neurosarcoidosis: a study of 54 cases. QJM. 2009;102(7):449–60.CrossRefPubMed
30.
go back to reference Shah R, Roberson GH, Cure JK. Correlation of MR imaging findings and clinical manifestations in neurosarcoidosis. AJNR Am J Neuroradiol. 2009;30(5):953–61.CrossRefPubMed Shah R, Roberson GH, Cure JK. Correlation of MR imaging findings and clinical manifestations in neurosarcoidosis. AJNR Am J Neuroradiol. 2009;30(5):953–61.CrossRefPubMed
31.
go back to reference Gascon-Bayarri J, Mana J, Martinez-Yelamos S, Murillo O, Rene R, Rubio F. Neurosarcoidosis: report of 30 cases and a literature survey. Eur J Intern Med. 2011;22(6):e125–32.CrossRefPubMed Gascon-Bayarri J, Mana J, Martinez-Yelamos S, Murillo O, Rene R, Rubio F. Neurosarcoidosis: report of 30 cases and a literature survey. Eur J Intern Med. 2011;22(6):e125–32.CrossRefPubMed
32.
go back to reference Nozaki K, Scott TF, Sohn M, Judson MA. Isolated neurosarcoidosis: case series in 2 sarcoidosis centers. Neurologist. 2012;18(6):373–7.CrossRefPubMed Nozaki K, Scott TF, Sohn M, Judson MA. Isolated neurosarcoidosis: case series in 2 sarcoidosis centers. Neurologist. 2012;18(6):373–7.CrossRefPubMed
33.
go back to reference Carlson ML, White Jr JR, Espahbodi M, Haynes DS, Driscoll CL, Aksamit AJ, Pawate S, Lane JI, Link MJ. Cranial base manifestations of neurosarcoidosis: a review of 305 patients. Otol Neurotol. 2015;36(1):156–66.PubMed Carlson ML, White Jr JR, Espahbodi M, Haynes DS, Driscoll CL, Aksamit AJ, Pawate S, Lane JI, Link MJ. Cranial base manifestations of neurosarcoidosis: a review of 305 patients. Otol Neurotol. 2015;36(1):156–66.PubMed
34.
go back to reference Gozubatik-Celik G, Uygunoglu U, Uluduz D, Atahan E, Musellim B, Saip S, Siva A. Diagnosis and treatment in neurosarcoidosis. Noropsikiyatri Arsivi. 2015;52(1):102–6.CrossRef Gozubatik-Celik G, Uygunoglu U, Uluduz D, Atahan E, Musellim B, Saip S, Siva A. Diagnosis and treatment in neurosarcoidosis. Noropsikiyatri Arsivi. 2015;52(1):102–6.CrossRef
35.
go back to reference Wegener S, Linnebank M, Martin R, Valavanis A, Weller M. Clinically isolated neurosarcoidosis: a recommended diagnostic path. Eur Neurol. 2015;73(1–2):71–7.CrossRefPubMed Wegener S, Linnebank M, Martin R, Valavanis A, Weller M. Clinically isolated neurosarcoidosis: a recommended diagnostic path. Eur Neurol. 2015;73(1–2):71–7.CrossRefPubMed
36.
go back to reference Leonhard SE, Fritz D, Van De Beek D, Brouwer MC. Neurosarcoidosis in a tertiary referral centre: a cross-sectional cohort study. Medicine (Baltimore). 2016;95(14), e3277.CrossRef Leonhard SE, Fritz D, Van De Beek D, Brouwer MC. Neurosarcoidosis in a tertiary referral centre: a cross-sectional cohort study. Medicine (Baltimore). 2016;95(14), e3277.CrossRef
37.
go back to reference Dispenzieri A, Buadi FK. A review of POEMS syndrome. Oncology (Williston Park). 2013;27(12):1242–50. Dispenzieri A, Buadi FK. A review of POEMS syndrome. Oncology (Williston Park). 2013;27(12):1242–50.
38.
39.
40.
go back to reference Petereit HF, Reske D, Tumani H, Jarius S, Markus Leweke F, Woitalla D, Pfister HW, Rubbert A. Soluble CSF interleukin 2 receptor as indicator of neurosarcoidosis. J Neurol. 2010;257(11):1855–63.CrossRefPubMed Petereit HF, Reske D, Tumani H, Jarius S, Markus Leweke F, Woitalla D, Pfister HW, Rubbert A. Soluble CSF interleukin 2 receptor as indicator of neurosarcoidosis. J Neurol. 2010;257(11):1855–63.CrossRefPubMed
41.
go back to reference Baughman RP, Drent M, Kavuru M, Judson MA, Costabel U, Du Bois R, Albera C, Brutsche M, Davis G, Donohue JF, et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 2006;174(7):795–802.CrossRefPubMed Baughman RP, Drent M, Kavuru M, Judson MA, Costabel U, Du Bois R, Albera C, Brutsche M, Davis G, Donohue JF, et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med. 2006;174(7):795–802.CrossRefPubMed
Metadata
Title
Clinical features, treatment and outcome in neurosarcoidosis: systematic review and meta-analysis
Authors
Daan Fritz
Diederik van de Beek
Matthijs C. Brouwer
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2016
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-016-0741-x

Other articles of this Issue 1/2016

BMC Neurology 1/2016 Go to the issue