Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Neurology
Published in: Journal of Neurology 9/2014

Open Access 01-09-2014 | Review

Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations

Authors: Seema Kalra, Alan Silman, Gulsen Akman-Demir, Saeed Bohlega, Afshin Borhani-Haghighi, Cris S. Constantinescu, Habib Houman, Alfred Mahr, Carlos Salvarani, Petros P. Sfikakis, Aksel Siva, Adnan Al-Araji

Published in: Journal of Neurology | Issue 9/2014

Login to get access

Abstract

Neuro-Behçet’s disease (NBD) is one of the more serious manifestations of Behçet’s disease (BD), which is a relapsing inflammatory multisystem disease with an interesting epidemiology. Though NBD is relatively uncommon, being potentially treatable, neurologists need to consider it in the differential diagnosis of inflammatory, infective, or demyelinating CNS disorders. Evidence-based information on key issues of NBD diagnosis and management is scarce, and planning for such studies is challenging. We therefore initiated this project to develop expert consensus recommendations that might be helpful to neurologists and other clinicians, created through an extensive literature review and wide consultations with an international advisory panel, followed by a Delphi exercise. We agreed on consensus criteria for the diagnosis of NBD with two levels of certainty in addition to recommendations on when to consider NBD in a neurological patient, and on the use of various paraclinical tests. The management recommendations included treatment of the parenchymal NBD and cerebral venous thrombosis, the use of disease modifying therapies, prognostic factors, outcome measures, and headache in BD. Future studies are needed to validate the proposed criteria and provide evidence-based treatments.
Appendix
Available only for authorised users
Literature
1.
Behçet H (1937) Uber residivierende, aphtose durch ein Virus verursachtes Geschwure am Mund, am Auge und an der Genitalien. Derm Wschr 105:1152–1157
2.
3.
Verity DH, Marr JE, Ohno S (1999) Behçet’s disease, the Silk Road and HLA-B51: historical and geographical perspectives. Tissue Antigens 54:213–220CrossRefPubMed
4.
Khairallah M, Accorinti M, Muccioli C, Kahloun R, Kempen JH et al (2012) Epidemiology of Behçet disease. Ocul Immunol Inflamm 20:324–335CrossRefPubMed
5.
Al-Araji A, Kidd DP (2009) Neuro-Behçet’s disease: epidemiology, clinical characteristics, and management. Lancet Neurol 8:192–204CrossRefPubMed
6.
7.
Strober BE, Clay Cather J, Cohen D et al (2012) A Delphi consensus approach to challenging case scenarios in moderate-to-severe psoriasis: Part 2. Dermatol Ther (Heidelb) 2:2. Epub 2012 Mar 30
8.
Sackett D, Rosenberg W, Muir Gray J, Haynes R, Richardson W (1996) Evidence based medicine: what it is and what it isn’t. Br Med J 312:71–77CrossRef
9.
Yazici H, Fresko I, Yurdakul S (2007) Behcet’s syndrome: disease manifestations, management, and advances in treatment. Nat Clin Pract Rheumatol 3:148–155CrossRefPubMed
10.
Hatemi G, Silman A, Bang D et al (2008) Management of Behcet’s disease: a systematic literature review for the EULAR evidence based recommendations for the management of Behcet’s disease. Ann Rheum Dis 67:1656–1662CrossRefPubMed
11.
Menthon M, LaValley MP, Maldini C, Guillevin L, Mahr A (2009) HLA-B51/B5 and the risk of Behçet disease: a systematic review and meta-analysis of case control genetic association studies. Arthritis Rheum 61:1287–1296CrossRefPubMed
12.
Maldini C, Lavalley MP, Cheminant M, de Menthon M, Mahr A (2012) Relationships of HLA-B51 or B5 genotype with Behcet’s disease clinical characteristics: systematic review and meta-analyses of observational studies. Rheumatol (Oxford) 51:887–900CrossRef
13.
International Study Group for Behçet’s Disease (1990) Criteria for diagnosis of Behcet’s disease. Lancet 335:1078–1080
14.
International Team for the Revision of the International Criteria for Behçet’s Disease (ITR-ICBD), Davatchi F, Assaad-Khalil S et al (2013) The international criteria for Behçet’s disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol. doi:10.​1111/​jdv.​12107
15.
Al-Fahad S, Al-Araji A (1999) Neuro-Behcet’s disease in Iraq: a study of 40 patients. J Neurol Sci 170:105–111CrossRefPubMed
16.
Akman-Demir G, Serdaroglu P, Tasci B (1999) Clinical patterns of neurological involvement in Behcet’s disease: evaluation of 200 patients. The Neuro-Behcet Study Group. Brain 122:2171–2182CrossRefPubMed
17.
Kidd D, Steuer A, Denman AM, Rudge P (1999) Neurological complications of Behcet’s syndrome. Brain 122:2183–2194CrossRefPubMed
18.
Siva A, Kantarci OH, Saip S et al (2001) Behcet’s disease: diagnostic and prognostic aspects of neurological involvement. J Neurol 248:95–103CrossRefPubMed
19.
Al-Araji A, Sharquie K, Al-Rawi Z (2003) Prevalence and patterns of neurological involvement in Behcet’s disease: a prospective study from Iraq. J Neurol Neurosurg Psychiatry 74:608–613PubMedCentralCrossRefPubMed
20.
Hentati F, Fredj M, Gharbi N, Hamida M (1993) Clinical and biological aspects of neuro-Behcet’s in Tunisia. In: Wechsler B, Godeau P (eds) Behcet’s disease. Elsevier, Amsterdam, pp 415–418
21.
Hirohata S, Kikuchi H, Sawada T et al (2012) Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis. Mod Rheumatol 22:405–413PubMedCentralCrossRefPubMed
22.
McDonald WI, Compston A, Edan G et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the international panel on the diagnosis of multiple sclerosis. Ann Neurol 50:121–127CrossRefPubMed
23.
Zajicek JP, Scolding NJ, Foster O et al (1998) Central nervous system sarcoidosis—diagnosis and management. QJM 92:103–117CrossRef
24.
Bohlega S, AlKawi MZ, Omer S et al (1993) Neuro-Behcet’s: clinical syndromes and prognosis. In: Wechsler B, Godeau P (eds) Behcet’s disease. Elsevier, Amsterdam, pp 429–433
25.
Borhani-Haghighi A, Pourmand R, Nikseresht AR (2005) Neuro-Behcet disease. A review. Neurologist 11:80–89CrossRefPubMed
26.
Siva A, Saip S (2009) The spectrum of nervous system involvement in Behçet’s syndrome and its differential diagnosis. J Neurol 56:513–529CrossRef
27.
Motomura S, Tabira T, Kuriowa Y et al (1998) A clinical comparative study of multiple sclerosis and neuro-Behçet syndrome. J Neurol Neurosurg Psychiatry 43:210–213CrossRef
28.
Coban O, Bahar S, Akman-Demir G et al (1999) Masked assessment of MRI findings: is it possible to differentiate neuro-Behçet’s disease from other central nervous system diseases? Neuroradiology 41:255–260CrossRefPubMed
29.
Yesilot N, Mutlu M, Gungor O, Baykal B, Serdaroglu P, Akman-Demir G (2007) Clinical characteristics and course of spinal cord involvement in Behçet’s disease. Eur J Neurol 14:729–737CrossRefPubMed
30.
Saruhan-Direskeneli G, Yentür SP, Mutlu M et al (2013) Intrathecal oligoclonal IgG bands are infrequently found in neuro-Behçet’s disease. Clin Exp Rheumatol 31(3 Suppl 77):25–27PubMed
31.
McLean BN, Miller D, Thompson EJ (1995) Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behçet’s disease involving the nervous system. J Neurol Neurosurg Psychiatry 58:548–554PubMedCentralCrossRefPubMed
32.
Reske D, Petereit HF, Heiss WD (2005) Difficulties in the differentiation of chronic inflammatory diseases of the central nervous system–value of cerebrospinal fluid analysis and immunological abnormalities in the diagnosis. Acta Neurol Scand 112:207–213CrossRefPubMed
33.
Joseph FG, Scolding NJ (2007) Neuro- Behçet’s disease in Caucasians: a study of 22 patients. Euro J Neurol 14:174–180CrossRef
34.
Al Kawi MZ, Bohlega S, Banna M (1997) MRI findings in neuro-Behcet’s disease. Neurology 41:405–408CrossRef
35.
Wechsler B, Dell’lsola B, Vidailhet M et al (1993) MRI in 31 patients with Behçet’s disease and neurological involvement: prospective study with clinical correlation. J Neurol Neurosurg Psychiatry 56:793–798PubMedCentralCrossRefPubMed
36.
Coban O, Bahar S, Akman-Demir G et al (1996) A controlled study of reliability and validity of MRI findings in neuro-Behçet’s disease. Neuroradiology 38:312–316CrossRefPubMed
37.
Koçer N, Islak C, Siva A, Saip S, Akman C, Kantarci O, Hamuryudan V (1999) CNS involvement in neuro-Behçet syndrome: an MR study. Am J Neuroradiol 20:1015–1024PubMed
38.
Lee SH, Yoon PH, Park SJ, Kim DI (2001) MRI findings in neuro-Behcet’s disease. Clin Radiol 56:485–494CrossRefPubMed
39.
Akman-Demir G, Bahar S, Coban O, Tasci B, Serdaroglu P (2003) Cranial MRI in Behçet’s disease: 134 examinations of 98 patients. Neuroradiology 45:851–859CrossRefPubMed
40.
Borhani-Haghighi A, Sarhadi S, Farahangiz S (2011) MRI findings of neuro-Behçet’s disease. Clin Rheumatol 30:765–770CrossRefPubMed
41.
Albayram S, Saip S, Hasiloglu ZI et al (2011) Evaluation of parenchymal neuro-behçet disease by using susceptibility-weighted imaging. Am J Neuroradiol 32:1050–1055CrossRefPubMed
42.
Yamakawa Y, Sugita Y, Nagatani T et al (1996) Interleukin-6 (IL-6) in patients with Behçet’s disease. J Dermatol Sci 11:189–195CrossRefPubMed
43.
Akman-Demir G, Erdem Tuzun, Sema Icoz et al (2008) Interleukin-6 in neuro-Behçet’s disease: association with disease subsets and long-term outcome. Cytokine 44:373–376CrossRefPubMed
44.
Hirohata S, Isshi K, Oguchi H et al (1997) Cerebrospinal fluid interleukin-6 in progressive neuro-Behçet’s syndrome. Clin Immunol Immunopathol 82:12–17CrossRefPubMed
45.
Saruhan-Direskeneli G, Yentur SP, Akman-Demir G, Isik N, Serdaroglu P (2003) Cytokines and chemokines in neuro-Behcet’s disease compared to multiple sclerosis and other neurological diseases. J Neuroimmunol 145:127–134CrossRefPubMed
46.
Fujikawa K, Aratake K, Kawakami A et al (2007) Successful treatment of refractory neuro-Behçet’s disease with infliximab: a case report to show its efficacy by magnetic resonance imaging, transcranial magnetic stimulation and cytokine profile. Ann Rheumat Dis 66:136–137PubMedCentralCrossRefPubMed
47.
Kikuchi H, Aramaki K, Hirohata S (2008) Effect of infliximab in progressive neuro-Behcet’s syndrome. J Neurol Sci 272:99–105CrossRefPubMed
48.
Budak-Alpdogan T, Demirçay, Alpdogan O et al (1998) Skin hyperreactivity of Behçet’s patients (pathergy reaction) is also positive in interferon alpha-treated chronic myeloid leukaemia patients, indicating similarly altered neutrophil functions in both disorders. Br J Rheumatol 37:1148–1151CrossRefPubMed
49.
Hatemi I, Hatemi G, Celik AF et al (2008) Frequency of pathergy phenomenon and other features of Behçet’s syndrome among patients with inflammatory bowel disease. Clin Exp Rheumatol 26(4 Suppl 50):S91–S95PubMed
50.
Yazici H, Chamberlain MA, Tuzun Y et al (1984) A comparative study of the pathergy among Turkish and British patients with Behcet’s disease. Ann Rheumc Dis 43:74–75CrossRef
51.
Gül A, Uyar FA, Inanc M et al (2001) Lack of association of HLA-B*51 with a severe disease course in Behçet’s disease. Rheumatology 40:668–672CrossRefPubMed
52.
Chang HK, Kim JU, Cheon KS, Chung HR, Lee KW, Lee IH (2001) HLA-B51 and its allelic types in association with Behçet’s disease and recurrent aphthous stomatitis in Korea. Clin Exp Rheumatol 19(5 Suppl 24):S31–S35PubMed
53.
Turker H, Terzi M, Bayrak O, Cengiz N, Onar M, Us O (2008) Visual evoked potentials in differential diagnosis of multiple sclerosis and neurobehcet’s disease. Tohoku J Exp Med 216:109–116CrossRefPubMed
54.
55.
Ozisik HI, Karlidag R, Hazneci E, Kizkin S, Ozcan C (2005) Cognitive event-related potential and neuropsychological findings in Behçet’s disease without neurological manifestations. Tohoku J Exp Med 206:15–22CrossRefPubMed
56.
Anlar O, Akdeniz N, Tombul T, Calka O, Bilgili SG (2006) Visual evoked potential findings in Behcet’s disease without neurological manifestations. Int J Neurosci 116:281–287CrossRefPubMed
57.
Yesilot N, Shehu M, Oktem-Tanor O, Serdaroglu P, Akman-Demir G (2006) Silent neurological involvement in Behçet’s disease. Clin Exp Rheumatol 24(5 Suppl 42):S65–S70PubMed
58.
Inaba G (1981) Clinical features of Neuro-Behçet’s syndrome. In: Inaba G (ed) Behçet’s Disease. University of Tokyo Press, Tokyo, pp 235–246
59.
Hayashi H, Fukuda Y, Kuwabara N (1981) Pathological studies on Neuro-Behçet’s disease. In: Inaba G (ed) Behçet’s disease. University of Tokyo Press, Tokyo, pp 197–211
60.
Hirohata S (2008) Histopathology of central nervous system lesions in Behçet’s disease. J Neurol Sci 267:41–47CrossRefPubMed
61.
Matsuo K, Yamada K, Nakajima K, Nakagawa M (2005) Neuro-Behçet disease mimicking brain tumor. Am J Neuroradiol 26:650–653PubMed
62.
Appenzeller S, de Castro R, Queiroz L de S et al (2006) Brain tumor-like lesion in Behçet disease. Rheumatol Int 26:577–580
63.
64.
Bertsias GK, Ioannidis JP, Aringer M, Bollen E, Bombardieri S, Bruce IN (2010) EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 69:2074–2082CrossRefPubMed
65.
Shugaiv E, Tüzün E, Mutlu M, Kiyat-Atamer A, Kurtuncu M, Akman-Demir G (2011) Mycophenolate mofetil as a novel immunosuppressant in the treatment of neuro-Behçet’s disease with parenchymal involvement: presentation of four cases. Clin Exp Rheumatol 29(4 Suppl 67):S64–S67PubMed
66.
Hirohata S, Suda H, Hashimoto T (1998) Low-dose weekly methotrexate for progressive neuropsychiatric manifestations in Behçet’s disease. J Neurol Sci 159:181–185CrossRefPubMed
67.
Kikuchi H, Aramaki K, Hirohata S (2003) Low dose MTX for progressive neuro-Behçet’s disease. A follow-up study for 4 years. Adv Exp Med Biol 528:575–578CrossRefPubMed
68.
O’Duffy JD, Robertson DM, Goldstein NP (1984) Chlorambucil in the treatment of uveitis and meningoencephalitis of Behçet’s disease. Am J Med 76:75–84CrossRefPubMed
69.
Ait Ben Haddou EH, Imounan F, Regragui W et al (2012) Neurological manifestations of Behçet’s disease: evaluation of 40 patients treated by cyclophosphamide. Rev Neurol (Paris) 168:344–349CrossRef
70.
Sarwar H, McGrath H Jr, Espinoza LR (2005) Successful treatment of long-standing neuro-Behçet’s disease with infliximab. J Rheumatol 32:181–183PubMed
71.
Pipitone N, Olivieri I, Padula A et al (2008) Infliximab for the treatment of Neuro-Behçet’s disease: a case series and review of the literature. Arthritis Rheum 59:285–290CrossRefPubMed
72.
Al-Araji A, Siva A, Saip S et al (2010) Treatment of Neuro-Behcet’s disease with infliximab. An international multi-centre case-series of 18 patients. Clin Exp Rheumatol 28 (Suppl 60): S119
73.
Fasano A, D’Agostino M, Caldarola G, Feliciani C, De Simone C (2011) Infliximab monotherapy in neuro-Behçet’s disease: four year follow-up in a long-standing case resistant to conventional therapies. J Neuroimmunol 239:105–107CrossRefPubMed
74.
Giardina A, Ferrante A, Ciccia F, Vadalà M, Giardina E, Triolo G (2011) One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Behçet’s disease refractory to standard immunosuppressive drugs. Rheumatol Int 31:33–37CrossRefPubMed
75.
Leccese P, D’Angelo S, Angela P, Coniglio G, Olivieri I (2010) Switching to adalimumab is effective in a case of neuro-Behçet’s disease refractory to infliximab. Clin Exp Rheumatol 28(4 Suppl 60):S102PubMed
76.
Olivieri I, Leccese P, D’Angelo S et al (2011) Efficacy of adalimumab in patients with Behçet’s disease unsuccessfully treated with infliximab. Clin Exp Rheumatol 29(4 Suppl 67):S54–S57PubMed
77.
Alty JE, Monaghan TM, Bamford JM (2007) A patient with neuro-Behçet’s disease is successfully treated with etanercept: further evidence for the value of TNF alpha blockade. Clin Neurol Neurosurg 109:279–281CrossRefPubMed
78.
Shapiro LS, Farrell J, Borhani-Haghighi A (2012) Tocilizumab treatment for neuro-Behcet’s disease, the first report. Clin Neurol Neurosurg 114:297–298CrossRefPubMed
79.
Nichols JC, Ince A, Akduman L, Mann ES (2001) Interferon-a2a treatment of neuro-Behçet disease. J Neuroophthalmol 21:109–111CrossRefPubMed
80.
Monastirli A, Chroni E, Georgiou S et al (2010) Interferon-α treatment for acute myelitis and intestinal involvement in severe Behçet’s disease. QJM 103:787–790CrossRefPubMed
81.
Arida A, Fragiadaki K, Giavri E, Sfikakis PP (2011) Anti-TNF agents for Behçet’s disease: analysis of published data on 369 patients. Semin Arthritis Rheum 41:61–70CrossRefPubMed
82.
Kotake S, Higashi K, Yoshikawa K, Sasamoto Y, Okamoto T, Matsuda H (1999) Central nervous system symptoms in patients with Behçet’s Behçet disease receiving ciclosporin therapy. Ophthalmology 106:586–589CrossRefPubMed
83.
Kato Y, Numaga J, Kato S et al (2001) Central nervous system in a population of Behçet’s disease patients with refractory uveitis treated with cyclosporine A. Clin Exp Ophthalmol 29:335–336CrossRef
84.
Kötter I, Günaydin I, Batra M et al (2006) CNS involvement occurs more frequently in patients with Behçet’s disease under cyclosporin A than under other medications–results of a retrospective analysis of 117 cases. Clin Rheumatol 25:482–486CrossRefPubMed
85.
Akman-Demir G, Ayranci O, Kurtuncu M, Vanli EN, Mutlu M, Tugal-Tutkun I (2008) Ciclosporin for Behçet’s uveitis: is it associated with an increased risk of neurological involvement? Clin Exp Rheumatol 26:S84–S90PubMed
86.
87.
Tayer-Shifman OE, Seyahi E, Nowatzky J, Ben-Chetrit E (2012) Major vessel thrombosis in Behçet’s disease: the dilemma of anticoagulant therapy—the approach of rheumatologists from different countries. Clin Exp Rheumatol 30:735–740PubMed
88.
89.
Calamia KT, Schirmer M, Melikoglu M (2011) Major vessel involvement in Behçet’s disease: an update. Curr Opin Rheumatol 23:24–31CrossRefPubMed
90.
Aguiar de Sousa D, Mestre T, Ferro JM (2011) Cerebral venous thrombosis in Behçet’s disease: a systematic review. J Neurol 258:719–727CrossRefPubMed
91.
Borhani-Haghighi A, Aflaki E, Ketabchi L (2008) The prevalence and characteristics of different types of headache in patients with Behçet’s disease, a case-control study. Headache 48:424–429CrossRefPubMed
92.
Aykutlu E, Baykan B, Akman-Demir G, Topcular B, Ertas M (2006) Headache in Behçet’s disease. Cephalalgia 26:180–186CrossRefPubMed
93.
Saip S, Siva A, Altintas A et al (2005) Headache in Behçet’s syndrome headache 45:911–919PubMed
94.
Rankin J (1957) Cerebral vascular accidents in patients over the age of 60. Scott Med J 2:200–215PubMed
95.
Bonita R, Beaglehole R (1988) Modification of Rankin scale: recovery of motor function after stroke. Stroke 19:1497–1500CrossRefPubMed
96.
Wilson JL, Hareendran A, Grant M et al (2002) Improving the assessment of outcomes in stroke: use of a structured interview to assign grades on the modified Rankin scale. Stroke 33:2243–2246CrossRefPubMed
97.
Wilson JL, Hareendran A, Hendry A et al (2005) Reliability of the modified Rankin scale across multiple raters: benefits of a structured interview. Stroke 36:777–781CrossRefPubMed
98.
Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452CrossRefPubMed
99.
Kurtuncu M, Tuzun E, Mutlu M, Pehlivan M, Serdaroglu P, Akman-Demir G (2008) Clinical patterns and course of neuro-Behçet’s disease: analysis of 354 patients comparing cases presented before and after 1990. Clin Exp Rheumatol 26(Suppl. 50):S1–S47
Metadata
Title
Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations
Authors
Seema Kalra
Alan Silman
Gulsen Akman-Demir
Saeed Bohlega
Afshin Borhani-Haghighi
Cris S. Constantinescu
Habib Houman
Alfred Mahr
Carlos Salvarani
Petros P. Sfikakis
Aksel Siva
Adnan Al-Araji
Publication date
01-09-2014
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 9/2014
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-013-7209-3

Other articles of this Issue 9/2014

Journal of Neurology 9/2014 Go to the issue

Original Communication

Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review

Original Communication

Arylsulphatase A activity in familial parkinsonism: a pathogenetic role?

Original Communication

Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity

Original Communication

Objective assessment of motor fatigue in multiple sclerosis: the Fatigue index Kliniken Schmieder (FKS)

Original Communication

Patterns of regional gray matter and white matter atrophy in cortical multiple sclerosis

Original Communication

Teriflunomide reduces relapses with sequelae and relapses leading to hospitalizations: results from the TOWER study