Advertisement

Distinguishing CNS neurosarcoidosis from multiple sclerosis and an approach to “overlap” cases

      Highlights

      • MS and neurosarcoidosis are conditions with potential for overlapping clinical and MRI features.
      • Tissue biopsy is not always possible to confirm diagnosis and guide targeted treatments.
      • Treatment of undifferentiated cases should favour agents that can treat both conditions.
      • Post-mortem histopathologic data in patients with dual diagnoses are lacking.

      Abstract

      Neurosarcoidosis is an important diagnosis to exclude in the work-up for suspected multiple sclerosis (MS). The distinction between the two conditions is usually possible due to characteristic clinical manifestations, magnetic resonance imaging (MRI) findings, and the results of other supportive investigations such as CT-PET. Definitive diagnosis can be made by histopathological examination, but this is not always practical. Misdiagnosis can occur when the clinical characteristics and MRI findings of both conditions overlap. Those patients with characteristic findings of MS but extraneural histopathological evidence of sarcoidosis are a particularly difficult diagnostic group. Diagnostic clarity is essential to inform treatment, especially as certain treatments for one disorder can exacerbate the other. This article summarises the clinical, laboratory and radiological findings that aid the clinician in distinguishing between the two conditions. It also discusses the literature on the potential for sarcoidosis and MS to co-exist in some patients, and how to approach the treatment of these “overlap” patients.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Neuroimmunology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Allen R.K.A.
        A review of angiotensin converting enzyme in health and disease.
        Sarcoidosis. 1991; 8: 95-100
        • Arun T.
        • Palace J.
        Effects of immunotherapies and clinical outcomes in neurosarcoidosis: a retrospective cohort study.
        J. Neurol. 2021 Jul; 268: 2466-2472https://doi.org/10.1007/s00415-021-10421-z
        • Arun T.
        • Pattison L.
        • Palace J.
        Distinguishing neurosarcoidosis from multiple sclerosis based on CSF analysis: a retrospective study.
        Neurology. 2020 Jun 16; 94: e2545-e2554https://doi.org/10.1212/WNL.0000000000009491
        • Awad A.
        • Hemmer B.
        • Hartung H.P.
        • Kieseier B.
        • Bennett J.L.
        • Stuve O.
        Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis.
        J. Neuroimmunol. 2010 Feb 26; 219: 1-7https://doi.org/10.1016/j.jneuroim.2009.09.002
        • Barnett M.H.
        • Prineas J.W.
        Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion.
        Ann. Neurol. 2004 Apr; 55: 458-468https://doi.org/10.1002/ana.20016
        • Barton J.L.
        • Garber J.Y.
        • Klistorner A.
        • Barnett M.H.
        The electrophysiological assessment of visual function in multiple sclerosis.
        Clin. Neurophysiol. Pract. 2019 May 8; 4: 90-96https://doi.org/10.1016/j.cnp.2019.03.002
        • Baughman R.P.
        • Janovcik J.
        • Ray M.
        • Sweiss N.
        • Lower E.E.
        Calcium and vitamin D metabolism in sarcoidosis.
        Sarcoidosis Vasc. Diffuse Lung Dis. 2013 Aug 1; 30: 113-120
        • Bhagwan S.
        • Bhagwan B.
        • Bhigjee A.I.
        The use of cladribine in neurosarcoidosis: a report of two cases.
        Clin. Neurol. Neurosurg. 2015 Sep; 136: 79-81
        • Bjornevik K.
        • Cortese M.
        • Healy B.C.
        • Kuhle J.
        • Mina M.J.
        • Leng Y.
        • Elledge S.J.
        • Niebuhr D.W.
        • Scher A.I.
        • Munger K.L.
        • Ascherio A.
        Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis.
        Science. 2022 Jan 21; 375: 296-301https://doi.org/10.1126/science.abj8222
        • Bloch-Michel E.
        • Nussenblatt R.B.
        International uveitis study group recommendations for the evaluation of intraocular inflammatory disease.
        Am J. Ophthalmol. 1987 Feb 15; 103: 234-235https://doi.org/10.1016/s0002-9394(14)74235-7
        • Bolaños I.
        • Lozano D.
        • Cantú C.
        Internuclear ophthalmoplegia: causes and long-term follow-up in 65 patients.
        Acta Neurol. Scand. 2004 Sep; 110: 161-165https://doi.org/10.1111/j.1600-0404.2004.00278.x
        • Bomprezzi R.
        • Pati S.
        • Chansakul C.
        • Vollmer T.
        A case of neurosarcoidosis successfully treated with rituximab.
        Neurology. 2010 Aug 10; 75: 568-570https://doi.org/10.1212/WNL.0b013e3181ec7ff9
        • Bot J.C.
        • Barkhof F.
        • Polman C.H.
        • Lycklama à Nijeholt G.J.
        • de Groot V.
        • Bergers E.
        • Ader H.J.
        • Castelijns J.A.
        Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.
        Neurology. 2004 Jan 27; 62: 226-233https://doi.org/10.1212/wnl.62.2.226
        • Bridel C.
        • Courvoisier D.S.
        • Vuilleumier N.
        • Lalive P.H.
        Cerebrospinal fluid angiotensin-converting enzyme for diagnosis of neurosarcoidosis.
        J. Neuroimmunol. 2015 Aug 15; : 1-3https://doi.org/10.1016/j.jneuroim.2015.05.020
        • Brownlee W.J.
        • Hardy T.A.
        • Fazekas F.
        • Miller D.H.
        Diagnosis of multiple sclerosis: progress and challenges.
        Lancet. 2017 Apr 1; 389: 1336-1346https://doi.org/10.1016/S0140-6736(16)30959-X
        • Burman J.
        • Raininko R.
        • Fagius J.
        Bilateral and recurrent optic neuritis in multiple sclerosis.
        Acta Neurol. Scand. 2011 Mar; 123: 207-210https://doi.org/10.1111/j.1600-0404.2010.01388.x
        • Burman J.
        • Zelano J.
        Epilepsy in multiple sclerosis: A nationwide population-based register study.
        Neurology. 2017 Dec 12; 89: 2462-2468https://doi.org/10.1212/WNL.0000000000004740
        • Casetta I.
        • Iuliano G.
        • Filippini G.
        Azathioprine for multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 2009 Feb; 80 (discussion 132): 131-132
        • Castillo-Trivino T.
        • Braithwaite D.
        • Bacchetti P.
        • Waubant E.
        Rituximab in relapsing and progressive forms of multiple sclerosis: a systematic review.
        PLoS One. 2013 Jul 2; 8e66308https://doi.org/10.1371/journal.pone.0066308
        • Chakravarty S.D.
        • Harris M.E.
        • Schreiner A.M.
        • Crow M.K.
        Sarcoidosis triggered by interferon-Beta treatment of multiple sclerosis: a case report and focused literature review.
        Semin. Arthritis Rheum. 2012 Oct; 42: 206-212https://doi.org/10.1016/j.semarthrit.2012.03.008
        • Chan M.
        • Hsiao E.
        Neurosarcoidosis on FET and FDG PET/CT.
        Clin. Nucl. Med. 2017 Mar; 42: 197-199https://doi.org/10.1097/RLU.0000000000001516
        • Christoforidis G.A.
        • Spickler E.M.
        • Recio M.V.
        • Mehta B.M.
        MR of CNS sarcoidosis: correlation of imaging features to clinical symptoms and response to treatment.
        AJNR Am. J. Neuroradiol. 1999 Apr; 20: 655-669
        • Cinetto F.
        • Compagno N.
        • Scarpa R.
        • Malipiero G.
        • Agostini C.
        Rituximab in refractory sarcoidosis: a single centre experience.
        Clin. Mol. Allergy. 2015; 13 (Published 2015 Sep 1): 19
        • Cirone D.
        • Cimino L.
        • Spinucci G.
        Uveitis and internuclear ophthalmoplegia as ocular manifestations of sarcoidosis.
        Saudi J. Ophthalmol. 2018 Apr–Jun; 32: 167-170https://doi.org/10.1016/j.sjopt.2017.12.003
        • Cohen Aubart F.
        • Bouvry D.
        • Galanaud D.
        • Dehais C.
        • Mathey G.
        • Psimaras D.
        • Haroche J.
        • Pottier C.
        • Hie M.
        • Mathian A.
        • Devilliers H.
        • Nunes H.
        • Valeyre D.
        • Amoura Z.
        Long-term outcomes of refractory neurosarcoidosis treated with infliximab.
        J. Neurol. 2017 May; 264: 891-897https://doi.org/10.1007/s00415-017-8444-9
        • Compston A.
        • Coles A.
        Multiple sclerosis.
        Lancet. 2008; 372: 1502-1517
        • Cotton F.
        • Weiner H.L.
        • Jolesz F.A.
        • Guttmann C.R.
        MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals.
        Neurology. 2003 Feb 25; 60: 640-646https://doi.org/10.1212/01.wnl.0000046587.83503.1e
        • Cremers J.P.
        • Drent M.
        • Bast A.
        • Shigemitsu H.
        • Baughman R.P.
        • Valeyre D.
        • Sweiss N.J.
        • Jansen T.L.
        Multinational evidence-based World Association of Sarcoidosis and Other Granulomatous Disorders recommendations for the use of methotrexate in sarcoidosis: integrating systematic literature research and expert opinion of sarcoidologists worldwide.
        Curr. Opin. Pulm. Med. 2013 Sep; 19: 545-561https://doi.org/10.1097/MCP.0b013e3283642a7a
        • da Silva C.J.
        • da Rocha A.J.
        • Mendes M.F.
        • Maia Jr., A.C.
        • Braga F.T.
        • Tilbery C.P.
        Trigeminal involvement in multiple sclerosis: magnetic resonance imaging findings with clinical correlation in a series of patients.
        Mult. Scler. 2005 Jun; 11: 282-285https://doi.org/10.1191/1352458505ms1186oa
        • Di Stadio A.
        • Dipietro L.
        • Ralli M.
        • Greco A.
        • Ricci G.
        • Messineo D.
        • Bernitsas E.
        Clinical and radiological findings of facial paralysis in multiple sclerosis.
        Mult. Scler Relat. Disord. 2020 Jan; 37101456https://doi.org/10.1016/j.msard.2019.101456
        • Ferriby D.
        • de Seze J.
        • Stojkovic T.
        • Hachulla E.
        • Wallaert B.
        • Destee A.
        • et al.
        Long-term follow-up of neurosarcoidosis.
        Neurology. 2001; 57: 927-929
        • Filippi M.
        • Rocca M.A.
        • Ciccarelli O.
        • De Stefano N.
        • Evangelou N.
        • Kappos L.
        • Rovira A.
        • Sastre-Garriga J.
        • Tintorè M.
        • Frederiksen J.L.
        • Gasperini C.
        • Palace J.
        • Reich D.S.
        • Banwell B.
        • Montalban X.
        • Barkhof F.
        • MAGNIMS Study Group
        MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines.
        Lancet Neurol. 2016 Mar; 15: 292-303
        • Filippini G.
        • Del Giovane C.
        • Vacchi L.
        • D’Amico R.
        • Di Pietrantonj C.
        • Beecher D.
        • Salanti G.
        Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.
        Cochrane Database Syst. Rev. 2013 Jun 6; CD008933https://doi.org/10.1002/14651858.CD008933.pub2
        • Flanagan E.P.
        Autoimmune myelopathies.
        Handb. Clin. Neurol. 2016; 133: 327-351https://doi.org/10.1016/B978-0-444-63432-0.00019-0
        • Flanagan E.P.
        • Hunt C.H.
        • Lowe V.
        • Mandrekar J.
        • Pittock S.J.
        • O’Neill B.P.
        • Keegan B.M.
        [(18)F]-fluorodeoxyglucose-positron emission tomography in patients with active myelopathy.
        Mayo Clin. Proc. Nov 2013; 88: 1204-1212https://doi.org/10.1016/j.mayocp.2013.07.019
        • Flanagan E.P.
        • Hinson S.R.
        • Lennon V.A.
        • Fang B.
        • Aksamit A.J.
        • Morris P.P.
        • Basal E.
        • Honorat J.A.
        • Alfugham N.B.
        • Linnoila J.J.
        • Weinshenker B.G.
        • Pittock S.J.
        • McKeon A.
        Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: analysis of 102 patients.
        Ann. Neurol. 2017 Feb; 81: 298-309https://doi.org/10.1002/ana.24881
        • Fritz D.
        • van de Beek D.
        • Brouwer M.C.
        Clinical features, treatment and outcome in neurosarcoidosis: systematic review and meta-analysis.
        BMC Neurol. 2016 Nov 15; 16: 220https://doi.org/10.1186/s12883-016-0741-x
        • Fujiwara K.
        • Furuta Y.
        • Fukuda S.
        Two cases of Heerfordt’s syndrome: a rare manifestation of sarcoidosis.
        Case Rep. Otolaryngol. 2016; 2016: 3642735https://doi.org/10.1155/2016/3642735
        • Galimberti F.
        • Fernandez A.P.
        Sarcoidosis following successful treatment of pemphigus vulgaris with rituximab: a rituximab-induced reaction further supporting B-cell contribution to sarcoidosis pathogenesis?.
        Clin. Exp. Dermatol. 2016 Jun; 41: 413-416https://doi.org/10.1111/ced.12793
        • Gelfand J.M.
        • Bradshaw M.J.
        • Stern B.J.
        • Clifford D.B.
        • Wang Y.
        • Cho T.A.
        • Koth L.L.
        • Hauser S.L.
        • Dierkhising J.
        • Vu N.
        • Sriram S.
        • Moses H.
        • Bagnato F.
        • Kaufmann J.A.
        • Ammah D.J.
        • Yohannes T.H.
        • Hamblin M.J.
        • Venna N.
        • Green A.J.
        • Pawate S.
        Infliximab for the treatment of CNS sarcoidosis: a multi-institutional series.
        Neurology. 2017 Nov 14; 89: 2092-2100https://doi.org/10.1212/WNL.0000000000004644
        • Gott P.S.
        • Kumar V.
        • Kadakia J.
        • Sharma O.P.
        Significance of multimodality evoked potential abnormalities in sarcoidosis.
        Sarcoidosis Vasc. Diffuse Lung Dis. 1997 Sep; 14: 159-164
        • Graf J.
        • Ringelstein M.
        • Lepka K.
        • Schaller J.
        • Quack H.
        • Hartung H.P.
        • Aktas O.
        • Albrecht P.
        Acute sarcoidosis in a multiple sclerosis patient after alemtuzumab treatment.
        Mult. Scler. 2018 Nov; 24: 1776-1778https://doi.org/10.1177/1352458518771276
        • Grunewald J.
        • Grutters J.C.
        • Arkema E.V.
        • Saketkoo L.A.
        • Moller D.R.
        • Müller-Quernheim J.
        Publisher correction: sarcoidosis.
        Nat. Rev. Dis. Primers. 2019 Jul 16; 5: 49https://doi.org/10.1038/s41572-019-0107-y. Erratum for: Nat Rev Dis Primers. 2019 Jul 4;5(1):45
        • Gullapalli D.
        • Phillips 2nd, L.H.
        Neurologic manifestations of sarcoidosis.
        Neurol. Clin. 2002 Feb; 20 (vi): 59-83
        • Hardy T.A.
        Pseudotumoral demyelinating lesions: diagnostic approach and long-term outcome.
        Curr. Opin. Neurol. 2019 Jun; 32: 467-474https://doi.org/10.1097/WCO.0000000000000683
        • Hardy T.A.
        • Reddel S.W.
        • Barnett M.H.
        • Palace J.
        • Lucchinetti C.F.
        • Weinshenker B.G.
        Atypical inflammatory demyelinating syndromes of the CNS.
        Lancet Neurol. 2016 Aug; 15: 967-981https://doi.org/10.1016/S1474-4422(16)30043-6
        • Hauser S.L.
        • Bar-Or A.
        • Comi G.
        • Giovannoni G.
        • Hartung H.P.
        • Hemmer B.
        • Lublin F.
        • Montalban X.
        • Rammohan K.W.
        • Selmaj K.
        • Traboulsee A.
        • Wolinsky J.S.
        • Arnold D.L.
        • Klingelschmitt G.
        • Masterman D.
        • Fontoura P.
        • Belachew S.
        • Chin P.
        • Mairon N.
        • Garren H.
        • Kappos L.
        OPERA I and OPERA II clinical investigators. Ocrelizumab versus interferon Beta-1a in relapsing multiple sclerosis.
        N. Engl. J. Med. 2017 Jan 19; 376: 221-234https://doi.org/10.1056/NEJMoa1601277
        • Heming M.
        • Lohmann L.
        • Schulte-Mecklenbeck A.
        • Brix T.
        • Gross C.C.
        • Wiendl H.
        • Klotz L.
        • Meyer Zu Hörste G.
        Leukocyte profiles in blood and CSF distinguish neurosarcoidosis from multiple sclerosis.
        J. Neuroimmunol. 2020 Apr 15; 577171https://doi.org/10.1016/j.jneuroim.2020.577171
        • Hilezian F.
        • Maarouf A.
        • Boutiere C.
        • Rico A.
        • Demortiere S.
        • Kerschen P.
        • Sene T.
        • Bensa-Koscher C.
        • Giannesini C.
        • Capron J.
        • Mekinian A.
        • Camdessanché J.P.
        • Androdias G.
        • Marignier R.
        • Collongues N.
        • Casez O.
        • Coclitu C.
        • Vaillant M.
        • Mathey G.
        • Ciron J.
        • Pelletier J.
        • Audoin B.
        Under the aegis of the French Multiple Sclerosis Society. TNF-α inhibitors used as steroid-sparing maintenance monotherapy in parenchymal CNS sarcoidosis.
        J. Neurol. Neurosurg. Psychiatry. 2021 Jun 8; 92: 890-896https://doi.org/10.1136/jnnp-2020-325665
        • ICHD-3
        The international classification of headache disorders, 3rd edition (beta version).
        Cephalalgia. 2013 Jul; 33: 629-808https://doi.org/10.1177/0333102413485658
        • James W.E.
        • Baughman R.
        Treatment of sarcoidosis: grading the evidence.
        Expert. Rev. Clin. Pharmacol. 2018 Jul; 11: 677-687https://doi.org/10.1080/17512433.2018.1486706
        • Joseph F.G.
        • Scolding N.J.
        Sarcoidosis of the nervous system.
        Pract. Neurol. 2007 Aug; 7: 234-244https://doi.org/10.1136/jnnp.2007.124263
        • Kawajiri M.
        • Mogi M.
        • Higaki N.
        • Matsuoka T.
        • Ohyagi Y.
        • Tsukuda K.
        • Kohara K.
        • Horiuchi M.
        • Miki T.
        • Kira J.I.
        Angiotensin-converting enzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis.
        Mult. Scler. 2009 Feb; 15: 262-265https://doi.org/10.1177/1352458508097923
        • Kidd D.P.
        Sarcoidosis of the central nervous system: clinical features, imaging, and CSF results.
        J. Neurol. 2018 Aug; 265: 1906-1915https://doi.org/10.1007/s00415-018-8928-2
        • Kidd D.P.
        • Burton B.J.
        • Graham E.M.
        • Plant G.T.
        Optic neuropathy associated with systemic sarcoidosis.
        Neurol. Neuroimmunol. Neuroinflamm. 2016 Aug 2; 3e270https://doi.org/10.1212/NXI.0000000000000270
        • Kingah P.
        • Alam M.
        • Chugh K.
        • Kamholz J.
        • Samavati L.
        Role of pulmonary evaluation in diagnosis of Neurosarcoidosis.
        Sarcoidosis Vasc. Diffuse Lung Dis. 2016 Oct 7; 33: 209-215
        • Klawiter E.C.
        • Benzinger T.
        • Roy A.
        • Naismith R.T.
        • Parks B.J.
        • Cross A.H.
        Spinal cord ring enhancement in multiple sclerosis.
        Arch. Neurol. Nov 2010; 67: 1395-1398https://doi.org/10.1001/archneurol.2010.271
        • Law L.Y.
        • Riminton D.S.
        • Nguyen M.
        • Barnett M.H.
        • Reddel S.W.
        • Hardy T.A.
        The spectrum of immune-mediated and inflammatory lesions of the brainstem: clues to diagnosis.
        Neurology. 2019 Aug 27; 93: 390-405https://doi.org/10.1212/WNL.0000000000008015
        • Lenercept Multiple Sclerosis Study Group
        TNF neutralization in MS: results of a randomized, placebo-controlled Mul- ticenter study. The Lenercept multiple sclerosis study group and the University of British Columbia MS/MRI analysis group.
        Neurology. 1999; 53: 457-465
        • Lopez-Sublet M.
        • Caratti di Lanzacco L.
        • Danser A.H.J.
        • Lambert M.
        • Elourimi G.
        • Persu A.
        Focus on increased serum angiotensin-converting enzyme level: from granulomatous diseases to genetic mutations.
        Clin. Biochem. 2018 Sep; 59: 1-8
        • Love B.
        • McCombe J.A.
        Anemia and sarcoidosis following treatment with alemtuzumab.
        Mult. Scler Relat. Disord. 2020 Nov; 46102526https://doi.org/10.1016/j.msard.2020.102526
        • MacLean H.J.
        • Abdoli M.
        Neurosarcoidosis as an MS mimic: the trials and tribulations of making a diagnosis.
        Mult. Scler Relat. Disord. 2015 Sep; 4: 414-429https://doi.org/10.1016/j.msard.2015.06.012
        • Maekawa T.
        • Goto Y.
        • Aoki T.
        • Hino A.
        • Oka H.
        • Yokoya S.
        • Fujii A.
        Acute central nervous system vasculitis as a manifestation of neurosarcoidosis: a case report and literature review.
        Radiol. Case Rep. 2020 Dec 14; 16: 410-414https://doi.org/10.1016/j.radcr.2020.11.047
        • Maggi P.
        • Absinta M.
        • Grammatico M.
        • Vuolo L.
        • Emmi G.
        • Carlucci G.
        • Spagni G.
        • Barilaro A.
        • Repice A.M.
        • Emmi L.
        • Prisco D.
        • Martinelli V.
        • Scotti R.
        • Sadeghi N.
        • Perrotta G.
        • Sati P.
        • Dachy B.
        • Reich D.S.
        • Filippi M.
        • Massacesi L.
        Central vein sign differentiates Multiple Sclerosis from central nervous system inflammatory vasculopathies.
        Ann. Neurol. 2018 Feb; 83: 283-294https://doi.org/10.1002/ana.25146
        • Magliozzi R.
        • Howell O.W.
        • Reeves C.
        • Roncaroli F.
        • Nicholas R.
        • Serafini B.
        • Aloisi F.
        • Reynolds R.
        A gradient of neuronal loss and meningeal inflammation in multiple sclerosis.
        Ann. Neurol. 2010 Oct; 68: 477-493https://doi.org/10.1002/ana.22230
        • Mealy M.A.
        • Whetstone A.
        • Orman G.
        • Izbudak I.
        • Calabresi P.A.
        • Levy M.
        Longitudinally extensive optic neuritis as an MRI biomarker distinguishes neuromyelitis optica from multiple sclerosis.
        J. Neurol. Sci. 2015; 355: 59-63https://doi.org/10.1016/j.jns.2015.05.013
        • Menezo Victor
        • Lobo Aires
        • Yeo Tun Kuan
        • du Bois Roland M.
        • Lightman Susan
        Ocular features in neurosarcoidosis.
        Ocul. Immunol. Inflamm. 2009; 17: 170-178https://doi.org/10.1080/09273940802687812
        • Miller D.H.
        • Kendall B.E.
        • Barter S.
        • Johnson G.
        • MacManus D.G.
        • Logsdail S.J.
        • Ormerod I.E.
        • McDonald W.I.
        Magnetic resonance imaging in central nervous system sarcoidosis.
        Neurology. 1988 Mar; 38: 378-383https://doi.org/10.1212/wnl.38.3.378
        • Mohan N.
        • Edwards E.T.
        • Cupps T.R.
        • Oliverio P.J.
        • Sandberg G.
        • Crayton H.
        • Richert J.R.
        • Siegel J.N.
        Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides.
        Arthritis Rheum. 2001 Dec; 44: 2862-2869https://doi.org/10.1002/1529-0131(200112)44:12<2862::aid-art474>3.0.co;2-w
        • Nowack U.
        • Gambichler T.
        • Hanefeld C.
        • Kastner U.
        • Altmeyer P.
        Successful treatment of recalcitrant cutaneous sarcoidosis with fumaric acid esters.
        BMC Dermatol. 2002 Dec 24; 2: 15https://doi.org/10.1186/1471-5945-2-15
        • Nowak D.A.
        • Widenka D.C.
        Neurosarcoidosis: a review of its intracranial manifestation.
        J. Neurol. 2001 May; 248: 363-372https://doi.org/10.1007/s004150170175
        • Nozaki K.
        • Judson M.A.
        Neurosarcoidosis: clinical manifestations, diagnosis and treatment.
        Presse Med. 2012 Jun; 41: e331-e348https://doi.org/10.1016/j.lpm.2011.12.017
        • Oksanen V.
        • Salmi T.
        Visual and auditory evoked potentials in the early diagnosis and follow-up of neurosarcoidosis.
        Acta Neurol. Scand. 1986; 74: 38-42
        • Orton S.M.
        • Herrera B.M.
        • Yee I.M.
        • Valdar W.
        • Ramagopalan S.V.
        • Sadovnick A.D.
        • Ebers G.C.
        • Canadian Collaborative Study Group
        Sex ratio of multiple sclerosis in Canada: a longitudinal study.
        Lancet Neurol. Nov 2006; 5: 932-936https://doi.org/10.1016/S1474-4422(06)70581-6
        • Parkes M.
        • Cortes A.
        • van Heel D.A.
        • Brown M.A.
        Genetic insights into common pathways and complex relationships among immune-mediated diseases.
        Nat. Rev. Genet. 2013 Sep; 14: 661-673https://doi.org/10.1038/nrg3502
        • Pawate S.
        • Moses H.
        • Sriram S.
        Presentations and outcomes of neurosarcoidosis: a study of 54 cases.
        QJM. 2009 Jul; 102: 449-460https://doi.org/10.1093/qjmed/hcp042
        • Petereit H.-F.
        • Reske D.
        • Tumani H.
        • Jarius S.
        • Markus Leweke F.
        • Woitalla D.
        • Pfister H.-W.
        • Rubbert A.
        Soluble CSF interleukin 2 receptor as indicator of neuro- sarcoidosis.
        J. Neurol. 2010; 257: 1855-1863https://doi.org/10.1007/s00415-010- 5623-3
        • Purves S.J.
        • Low M.D.
        • Galloway J.
        • Reeves B.
        A comparison of visual, brainstem auditory, and somatosensory evoked potentials in multiple sclerosis.
        Can. J. Neurol. Sci. 1981 Feb; 8: 15-19https://doi.org/10.1017/s0317167100042773
        • Putzki N.
        • Pfriem A.
        • Limmroth V.
        • Yaldizli O.
        • Tettenborn B.
        • Diener H.C.
        • Katsarava Z.
        Prevalence of migraine, tension-type headache and trigeminal neuralgia in multiple sclerosis.
        Eur. J. Neurol. 2009 Feb; 16: 262-267https://doi.org/10.1111/j.1468-1331.2008.02406.x
        • Rajoriya N.
        • Wotton C.J.
        • Yeates D.G.
        • Travis S.P.
        • Goldacre M.J.
        Immune-mediated and chronic inflammatory disease in people with sarcoidosis: disease associations in a large UK database.
        Postgrad. Med. J. 2009 May; 85: 233-237https://doi.org/10.1136/pgmj.2008.067769
        • Rakusa M.
        • Cano S.J.
        • Porter B.
        • Riazi A.
        • Thompson A.J.
        • Chataway J.
        • Hardy T.A.
        A predictive model for corticosteroid response in individual patients with MS relapses.
        PLoS One. 2015 Mar 18; 10e0120829https://doi.org/10.1371/journal.pone.0120829
        • Ramanathan S.
        • Fraser C.
        • Curnow S.R.
        • Ghaly M.
        • Leventer R.J.
        • Lechner-Scott J.
        • Henderson A.
        • Reddel S.
        • Dale R.C.
        • Brilot F.
        Uveitis and optic perineuritis in the context of myelin oligodendrocyte glycoprotein antibody seropositivity.
        Eur. J. Neurol. 2019 Aug; 26: 1137-e75https://doi.org/10.1111/ene.13932
        • Ramirez-Lassepas M.
        • Tulloch J.W.
        • Quinones M.R.
        • Snyder B.D.
        Acute radicular pain as a presenting symptom in multiple sclerosis.
        Arch. Neurol. 1992 Mar; 49: 255-258https://doi.org/10.1001/archneur.1992.00530270069020
        • Ramos-Casals M.
        • Pérez-Alvarez R.
        • Kostov B.
        • Gómez-de-la-Torre R.
        • Feijoo-Massó C.
        • Chara-Cervantes J.
        • Pinilla B.
        • González-García A.
        • Garcia-Morillo J.S.
        • López-Dupla M.
        • De-Escalante B.
        • Rascón J.
        • Perez-Guerrero P.
        • Bonet M.
        • Cruz-Caparrós G.
        • Alguacil A.
        • Callejas J.L.
        • Calvo E.
        • Soler C.
        • Robles A.
        • de Miguel-Campo B.
        • Oliva-Nacarino P.
        • Estela-Herrero J.
        • Pallarés L.
        • Brito-Zerón P.
        • Blanco Y.
        • SarcoGEAS-SEMI Registry
        Clinical characterization and outcomes of 85 patients with neurosarcoidosis.
        Sci. Rep. 2021 Jul 2; 11: 13735https://doi.org/10.1038/s41598-021-92967-6
        • Relling M.V.
        • Schwab M.
        • Whirl-Carrillo M.
        • Suarez-Kurtz G.
        • Pui C.H.
        • Stein C.M.
        • Moyer A.M.
        • Evans W.E.
        • Klein T.E.
        • Antillon-Klussmann F.G.
        • Caudle K.E.
        • Kato M.
        • Yeoh A.E.J.
        • Schmiegelow K.
        • Yang J.J.
        Clinical pharmacogenetics implementation consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update.
        Clin. Pharmacol. Ther. 2019 May; 105: 1095-1105https://doi.org/10.1002/cpt.1304
        • Rinaldi S.
        • Davies A.
        • Fehmi J.
        • Beadnall H.N.
        • Wang J.
        • Hardy T.A.
        • Barnett M.H.
        • Broadley S.A.
        • Waters P.
        • Reddel S.W.
        • Irani S.R.
        • Brilot F.
        • Dale R.C.
        • Ramanathan S.
        • Australian and New Zealand MOG Study Group
        Overlapping central and peripheral nervous system syndromes in MOG antibody-associated disorders.
        Neurol. Neuroimmunol. Neuroinflamm. 2020 Dec 3; 8: e924https://doi.org/10.1212/NXI.0000000000000924
        • Sahraian M.A.
        • Moghadasi A.N.
        • Owji M.
        • Maboudi M.
        • Kosari F.
        • McGee J.C.
        • Minagar A.
        Cutaneous and pulmonary sarcoidosis following treatment of multiple sclerosis with interferon-β-1b: a case report.
        J. Med. Case Rep. 2013 Dec 13; : 270https://doi.org/10.1186/1752-1947-7-270
        • Sakushima K.
        • Yabe I.
        • Nakano F.
        • Yoshida K.
        • Tajima Y.
        • Houzen H.
        • Maruo Y.
        • Sasaki H.
        Clinical features of spinal cord sarcoidosis: analysis of 17 neurosarcoidosis patients.
        J. Neurol. Dec 2011; 258: 2163-2167https://doi.org/10.1007/s00415-011-6080-3
        • Sánchez P.
        • Chan F.
        • Hardy T.A.
        Tumefactive demyelination: updated perspectives on diagnosis and management.
        Expert. Rev. Neurother. 2021 Sep; 21: 1005-1017https://doi.org/10.1080/14737175.2021.1971077
        • Santos E.
        • Shaunak S.
        • Renowden S.
        • Scolding N.J.
        Treatment of refractory neurosarcoidosis with infliximab.
        J. Neurol. Neurosurg. Psychiatry. 2010 Mar; 81: 241-246https://doi.org/10.1136/jnnp.2008.149989
        • Schweisfurth H.
        • Schiöberg-Schiegnitz S.
        • Kuhn W.
        • Parusel B.
        Angiotensin I converting enzyme in cerebrospinal fluid of patients with neurological diseases.
        Klin. Wochenschr. 1987 Oct 15; 65: 955-958https://doi.org/10.1007/BF01717829
        • Scott T.F.
        Neurosarcoidosis mimicry of MS: clues from cases with CNS tissue diagnosis.
        J. Neurol. Sci. 2021 Oct 15; 429117621https://doi.org/10.1016/j.jns.2021.117621
        • Scott T.F.
        • Yandora K.
        • Kunschner L.J.
        • Schramke C.
        Neurosarcoidosis mimicry of multiple sclerosis: clinical, laboratory, and imaging characteristics.
        Neurologist. 2010 Nov; 16: 386-389https://doi.org/10.1097/NRL.0b013e3181b287df
        • Sève P.
        • Pacheco Y.
        • Durupt F.
        • Jamilloux Y.
        • Gerfaud-Valentin M.
        • Isaac S.
        • Boussel L.
        • Calender A.
        • Androdias G.
        • Valeyre D.
        • El Jammal T.
        Sarcoidosis: a clinical overview from symptoms to diagnosis.
        Cells. 2021 Mar 31; 10: 766
        • Shah R.
        • Roberson G.H.
        • Curé J.K.
        Correlation of MR imaging findings and clinical manifestations in neurosarcoidosis.
        AJNR Am. J. Neuroradiol. 2009 May; 30: 953-961https://doi.org/10.3174/ajnr.A1470
        • Smith J.K.
        • Matheus M.G.
        • Castillo M.
        Imaging manifestations of neurosarcoidosis.
        AJR Am. J. Roentgenol. 2004 Feb; 182: 289-295https://doi.org/10.2214/ajr.182.2.1820289
        • Smith G.
        • Brownell I.
        • Sanchez M.
        • Prystowsky S.
        Advances in the genetics of sarcoidosis.
        Clin. Genet. May 2008; 73: 401-412https://doi.org/10.1111/j.1399-0004.2008.00970.x
        • Sokic D.V.
        • Stojsavljevic N.
        • Drulovic J.
        • Dujmovic I.
        • Mesaros S.
        • Ercegovac M.
        • Peric V.
        • Dragutinovic G.
        • Levic Z.
        Seizures in multiple sclerosis.
        Epilepsia. 2001 Jan; 42 (PMID: 11207788): 72-79https://doi.org/10.1046/j.1528-1157.2001.48699.x
        • Stern B.J.
        • Krumholz A.
        • Johns C.
        • Scott P.
        • Nissim J.
        Sarcoidosis and its neurological manifestations.
        Arch. Neurol. 1985 Sep; 42: 909-917https://doi.org/10.1001/archneur.1985.04060080095022
        • Stern B.J.
        • Royal 3rd, W.
        • Gelfand J.M.
        • Clifford D.B.
        • Tavee J.
        • Pawate S.
        • Berger J.R.
        • Aksamit A.J.
        • Krumholz A.
        • Pardo C.A.
        • Moller D.R.
        • Judson M.A.
        • Drent M.
        • Baughman R.P.
        Definition and consensus diagnostic criteria for Neurosarcoidosis: from the Neurosarcoidosis consortium consensus group.
        JAMA Neurol. 1 Dec 2018; 75: 1546-1553https://doi.org/10.1001/jamaneurol.2018.2295
        • Streletz L.J.
        • Chambers R.A.
        • Bae S.H.
        • Israel H.L.
        Visual evoked potentials in sarcoidosis.
        Neurology. 1981; 31: 1545-1549
        • Sundaram S.
        • Nair S.S.
        • Jaganmohan D.
        • Unnikrishnan G.
        • Nair M.
        Relapsing lumbosacral myeloradiculitis: an unusual presentation of MOG antibody disease.
        Mult. Scler. J. 2020 Apr; 26: 509-511https://doi.org/10.1177/1352458519840747
        • Sweiss N.J.
        • Lower E.E.
        • Mirsaeidi M.
        • Dudek S.
        • Garcia J.G.
        • Perkins D.
        • Finn P.W.
        • Baughman R.P.
        Rituximab in the treatment of refractory pulmonary sarcoidosis.
        Eur. Respir. J. 2014 May; 43 (Epub 2014 Jan 31): 1525-1528https://doi.org/10.1183/09031936.00224513
        • Takai Y.
        • Misu T.
        • Nakashima I.
        • Takahashi T.
        • Itoyama Y.
        • Fujihara K.
        • et al.
        Two cases of lumbosacral myeloradiculitis with anti-aquaporin-4 antibody.
        Neurology. 2012; 79: 1826-1828https://doi.org/10.1212/WNL.0b013e3182703ff7
        • Tana C.
        • Wegener S.
        • Borys E.
        • Pambuccian S.
        • Tchernev G.
        • Tana M.
        • Giamberardino M.A.
        • Silingardi M.
        Challenges in the diagnosis and treatment of neurosarcoidosis.
        Ann. Med. 2015; 47: 576-591https://doi.org/10.3109/07853890.2015.1093164
        • Tana C.
        • Donatiello I.
        • Caputo A.
        • Tana M.
        • Naccarelli T.
        • Mantini C.
        • Ricci F.
        • Ticinesi A.
        • Meschi T.
        • Cipollone F.
        • Giamberardino M.A.
        Clinical features, histopathology and differential diagnosis of sarcoidosis.
        Cells. 2021 Dec 26; 11: 59https://doi.org/10.3390/cells11010059
        • Tebben P.J.
        • Singh R.J.
        • Kumar R.
        Vitamin D-mediated hypercalcemia: mechanisms, diagnosis, and treatment.
        Endocr. Rev. 2016 Oct; 37: 521-547https://doi.org/10.1210/er.2016-1070
        • Thömke F.
        • Lensch E.
        • Ringel K.
        • Hopf H.C.
        Isolated cranial nerve palsies in multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 1997 Nov; 63: 682-685https://doi.org/10.1136/jnnp.63.5.682
        • Thompson A.J.
        • Banwell B.L.
        • Barkhof F.
        • Carroll W.M.
        • Coetzee T.
        • Comi G.
        • Correale J.
        • Fazekas F.
        • Filippi M.
        • Freedman M.S.
        • Fujihara K.
        • Galetta S.L.
        • Hartung H.P.
        • Kappos L.
        • Lublin F.D.
        • Marrie R.A.
        • Miller A.E.
        • Miller D.H.
        • Montalban X.
        • Mowry E.M.
        • Sorensen P.S.
        • Tintoré M.
        • Traboulsee A.L.
        • Trojano M.
        • Uitdehaag B.M.J.
        • Vukusic S.
        • Waubant E.
        • Weinshenker B.G.
        • Reingold S.C.
        • Cohen J.A.
        Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.
        Lancet Neurol. 2018 Feb; 17: 162-173https://doi.org/10.1016/S1474-4422(17)30470-2
        • Tikoo R.K.
        • Kupersmith M.J.
        • Finlay J.L.
        Treatment of refractory neurosarcoidosis with cladribine.
        N. Engl. J. Med. 2004 Apr 22; 350: 1798-1799https://doi.org/10.1056/NEJMc032345
        • Tillema J.M.
        • Pirko I.
        Neuroradiological evaluation of demyelinating disease.
        Ther. Adv. Neurol. Disord. 2013 Jul; 6: 249-268https://doi.org/10.1177/1756285613478870
        • Tong D.
        • Manolios N.
        • Howe G.
        • Spencer D.
        New onset sarcoid-like granulomatosis developing during anti-TNF therapy: an under-recognised complication.
        Intern. Med. J. 2012 Jan; 42: 89-94https://doi.org/10.1111/j.1445-5994.2011.02612.x
        • Toosy A.T.
        • Mason D.F.
        • Miller D.H.
        Optic neuritis.
        Lancet Neurol. 2014 Jan; 13: 83-99https://doi.org/10.1016/S1474-4422(13)70259-X
        • Torgauten H.M.
        • Myhr K.M.
        • Wergeland S.
        • Bø L.
        • Aarseth J.H.
        • Torkildsen Ø.
        Safety and efficacy of rituximab as first- and second line treatment in multiple sclerosis – a cohort study.
        Mult. Scler J. Exp. Transl. Clin. 2021 Jan 31; 7 (2055217320973049)https://doi.org/10.1177/2055217320973049
        • Trip S.A.
        • Miller D.H.
        Imaging in multiple sclerosis.
        J. Neurol. Neurosurg. Psychiatry. 2005 Sep; 76: iii11-iii18https://doi.org/10.1136/jnnp.2005.073213
        • Triplett J.D.
        • Buzzard K.A.
        • Lubomski M.
        • Riminton D.S.
        • Barnett M.H.
        • Welgampola M.S.
        • Halmagyi G.M.
        • Nguyen M.
        • Landau K.
        • Lee A.G.
        • Plant G.T.
        • Fraser C.L.
        • Reddel S.W.
        • Hardy T.A.
        Immune-mediated conditions affecting the brain, eye and ear (BEE syndromes).
        J. Neurol. Neurosurg. Psychiatry. 2019 Aug; 90: 882-894https://doi.org/10.1136/jnnp-2018-319002
        • Tyshkov C.
        • Pawate S.
        • Bradshaw M.J.
        • Kimbrough D.J.
        • Chitnis T.
        • Gelfand J.M.
        • Ryerson L.Z.
        • Kister I.
        Multiple sclerosis and sarcoidosis: a case for coexistence.
        Neurol. Clin Pract. 2019 Jun; 9: 218-227https://doi.org/10.1212/CPJ.0000000000000629
        • van der Mei I.A.
        • Simpson Jr., S.
        • Stankovich J.
        • Taylor B.V.
        Individual and joint action of environmental factors and risk of MS.
        Neurol. Clin. 2011 May; 29: 233-255https://doi.org/10.1016/j.ncl.2010.12.007
        • Wallin M.T.
        • Culpepper W.J.
        • Nichols E.
        • Bhutta Z.A.
        • Gebrehiwot T.T.
        • Hay S.I.
        • et al.
        • GBD 2016 Multiple Sclerosis Collaborators
        Global, regional, and national burden of multiple sclerosis 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.
        Lancet Neurol. 2019 Mar; 18: 269-285https://doi.org/10.1016/S1474-4422(18)30443-5
        • Walsh J.C.
        • Garrick R.
        • Cameron J.
        • McLeod J.G.
        Evoked potential changes in clinically definite multiple sclerosis: a two year follow up study.
        J. Neurol. Neurosurg. Psychiatry. 1982 Jun; 45: 494-500https://doi.org/10.1136/jnnp.45.6.494
        • Wattjes M.P.
        • Ciccarelli O.
        • Reich D.S.
        • Banwell B.
        • de Stefano N.
        • Enzinger C.
        • Fazekas F.
        • Filippi M.
        • Frederiksen J.
        • Gasperini C.
        • Hacohen Y.
        • Kappos L.
        • Li D.K.B.
        • Mankad K.
        • Montalban X.
        • Newsome S.D.
        • Oh J.
        • Palace J.
        • Rocca M.A.
        • Sastre-Garriga J.
        • Tintoré M.
        • Traboulsee A.
        • Vrenken H.
        • Yousry T.
        • Barkhof F.
        • Rovira À.
        • Magnetic Resonance Imaging in Multiple Sclerosis study group; Consortium of Multiple Sclerosis Centres; North American Imaging in Multiple Sclerosis Cooperative MRI guidelines working group
        2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis.
        Lancet Neurol. 2021 Aug; 20: 653-670
        • Wiendl H.
        • Gold R.
        • Berger T.
        • Derfuss T.
        • Linker R.
        • Mäurer M.
        • Aktas O.
        • Baum K.
        • Berghoff M.
        • Bittner S.
        • Chan A.
        • Czaplinski A.
        • Deisenhammer F.
        • Di Pauli F.
        • Du Pasquier R.
        • Enzinger C.
        • Fertl E.
        • Gass A.
        • Gehring K.
        • Gobbi C.
        • Goebels N.
        • Guger M.
        • Haghikia A.
        • Hartung H.P.
        • Heidenreich F.
        • Hoffmann O.
        • Kallmann B.
        • Kleinschnitz C.
        • Klotz L.
        • Leussink V.I.
        • Leutmezer F.
        • Limmroth V.
        • Lünemann J.D.
        • Lutterotti A.
        • Meuth S.G.
        • Meyding-Lamadé U.
        • Platten M.
        • Rieckmann P.
        • Schmidt S.
        • Tumani H.
        • Weber F.
        • Weber M.S.
        • Zettl U.K.
        • Ziemssen T.
        • Zipp F.
        • “Multiple Sclerosis Therapy Consensus Group” (MSTCG)
        Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper).
        Ther. Adv. Neurol. Disord. 2021 Aug 18; (17562864211039648)https://doi.org/10.1177/17562864211039648
        • Willis M.D.
        • Hope-Gill B.
        • Flood-Page P.
        • Joseph F.
        • Needham E.
        • Jones J.
        • Coles A.
        • Robertson N.P.
        Sarcoidosis following alemtuzumab treatment for multiple sclerosis.
        Mult. Scler. 2018 Nov; 24: 1779-1782https://doi.org/10.1177/1352458518790391
        • Zadro I.
        • Barun B.
        • Habek M.
        • Brinar V.V.
        Isolated cranial nerve palsies in multiple sclerosis.
        Clin. Neurol. Neurosurg. 2008 Nov; 110: 886-888https://doi.org/10.1016/j.clineuro.2008.02.009
        • Zajicek J.P.
        • Scolding N.J.
        • Foster O.
        • Rovaris M.
        • Evanson J.
        • Moseley I.F.
        • Scadding J.W.
        • Thompson E.J.
        • Chamoun V.
        • Miller D.H.
        • McDonald W.I.
        • Mitchell D.
        Central nervous system sarcoidosis–diagnosis and management.
        QJM. 1999 Feb; 92: 103-117https://doi.org/10.1093/qjmed/92.2.103
        • Zalewski N.L.
        • Krecke K.N.
        • Weinshenker B.G.
        • Aksamit A.J.
        • Conway B.L.
        • McKeon A.
        • Flanagan E.P.
        Central canal enhancement and the trident sign in spinal cord sarcoidosis.
        Neurology. 2016 Aug 16; 87: 743-744https://doi.org/10.1212/WNL.0000000000002992
        • Zein G.
        • Berta A.
        • Foster C.S.
        Multiple sclerosis-associated uveitis.
        Ocul. Immunol. Inflamm. 2004 Jun; 12: 137-142https://doi.org/10.1080/09273940490895344
        • Zella S.
        • Kneiphof J.
        • Haghikia A.
        • Gold R.
        • Woitalla D.
        • Thöne J.
        Successful therapy with rituximab in three patients with probable neurosarcoidosis.
        Ther. Adv. Neurol. Disord. 2018 Oct 26; (1756286418805732)https://doi.org/10.1177/1756286418805732
        • Zouboulis C.C.
        • Lippert U.
        • Karagiannidis I.
        Multi-organ sarcoidosis treatment with fumaric acid esters: a case report and review of the literature.
        Dermatology. 2014; 228 (Epub 2014 Mar 27. PMID: 24686198): 202-206https://doi.org/10.1159/000358428