Neurosarcoidosis: Diagnosis and Management

ABSTRACT

Sarcoidosis is a multisystemic inflammatory granulomatous disease that affects both the central and peripheral nervous system. The neurological manifestations depend on the areas of the neuroaxis affected. In the brain, patients with neurosarcoidosis have leptomeningeal and intraparenchymal infiltration of granulomas that leads to, for example, cranial nerve palsies, basal meningitis, and endocrine dysfunction. It can cause peripheral neuropathies such as mononeuritis multiplex and sensorimotor polyneuropathy as well as radiculopathy and myopathy. Diagnosis and management of patients with neurosarcoidosis are challenging given that the gold standard is tissue-proven biopsy, which, in most cases of neurological illness, is difficult to obtain. Treatment strategies have not been rigorously evaluated but corticosteroids are considered the drug of choice. Other immunosuppressant agents such as cyclophosphamide, mycophenolate mofetil, and infliximab are efficacious in the treatment of neurosarcoidosis.

KEYWORDS

Neurosarcoidosis - inflammation - immunosuppression

REFERENCES

• 1 James D G, Sharma O P. Neurosarcoidosis.  Proc R Soc Med. 1967;  60(11 Part 1) 1169-1170
• 2 Burns T M. Neurosarcoidosis.  Arch Neurol. 2003;  60 1166-1168
• 3 Schwendimann R N, Harris M K, Elliott D G et al.. Neurosarcoidosis: Clinical Features, Diagnosis, and Management.  Am J Ther. 2009 May 19;  , [Epub ahead of print]
• 4 Nowak D A, Widenka D C. Neurosarcoidosis: a review of its intracranial manifestation.  J Neurol. 2001;  248 363-372
• 5 Iwai K, Tachibana T, Takemura T, Matsui Y, Kitaichi M, Kawabata Y. Pathological studies on sarcoidosis autopsy, I: Epidemiological features of 320 cases in Japan.  Acta Pathol Jpn. 1993;  43 372-376
• 6 Hosoda Y SS, Sasagawa S, Yasuda N. Epidemiology of sarcoidosis: new frontiers to explore.  Curr Opin Pulm Med. 2002;  8 424-428
• 7 Rybicki B A, Major M, Popovich Jr J, Maliarik M J, Iannuzzi M C. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization.  Am J Epidemiol. 1997;  145 234-241
• 8 Iannuzzi M C, Rybicki B A, Teirstein A S. Sarcoidosis.  N Engl J Med. 2007;  357 2153-2165
• 9 Brewerton D A, Cockburn C, James D C, James D G, Neville E. HLA antigens in sarcoidosis.  Clin Exp Immunol. 1977;  27 227-229
• 10 Rossman M D, Thompson B, Frederick M ACCESS Group et al. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites.  Am J Hum Genet. 2003;  73 720-735
• 11 Iannuzzi M C, Maliarik M J, Poisson L M, Rybicki B A. Sarcoidosis susceptibility and resistance HLA-DQB1 alleles in African Americans.  Am J Respir Crit Care Med. 2003;  167 1225-1231
• 12 Newman L S, Rose C S, Bresnitz E A ACCESS Research Group et al. A case control etiologic study of sarcoidosis: environmental and occupational risk factors.  Am J Respir Crit Care Med. 2004;  170 1324-1330
• 13 Gorham E D, Garland C F, Garland F C, Kaiser K, Travis W D, Centeno J A. Trends and occupational associations in incidence of hospitalized pulmonary sarcoidosis and other lung diseases in Navy personnel: a 27-year historical prospective study, 1975-2001.  Chest. 2004;  126 1431-1438
• 14 Kajdasz D K, Lackland D T, Mohr L C, Judson M A. A current assessment of rurally linked exposures as potential risk factors for sarcoidosis.  Ann Epidemiol. 2001;  11 111-117
• 15 Rybicki B A, Amend K L, Maliarik M J, Iannuzzi M C. Photocopier exposure and risk of sarcoidosis in African-American sibs.  Sarcoidosis Vasc Diffuse Lung Dis. 2004;  21 49-55
• 16 Kucera G P, Rybicki B A, Kirkey K L et al.. Occupational risk factors for sarcoidosis in African-American siblings.  Chest. 2003;  123 1527-1535
• 17 Hoitsma E, Faber C G, Drent M, Sharma O P. Neurosarcoidosis: a clinical dilemma.  Lancet Neurol. 2004;  3 397-407
• 18 Zajicek J P, Scolding N J, Foster O et al.. Central nervous system sarcoidosis—diagnosis and management.  QJM. 1999;  92 103-117
• 19 Plotkin G R, Patel B R. Neurosarcoidosis presenting as chronic lymphocytic meningitis.  Pa Med. 1986;  89 36-37
• 20 Lower E E, Weiss K L. Neurosarcoidosis.  Clin Chest Med. 2008;  29 475-492 ix
• 21 Murialdo G, Tamagno G. Endocrine aspects of neurosarcoidosis.  J Endocrinol Invest. 2002;  25 650-662
• 22 Konrad D, Gartenmann M, Martin E, Schoenle E J. Central diabetes insipidus as the first manifestation of neurosarcoidosis in a 10-year-old girl.  Horm Res. 2000;  54 98-100
• 23 Tamagno G, Murialdo G. Amenorrhea-galactorrhea syndrome as an uncommon manifestation of isolated neurosarcoidosis.  Ann Ital Med Int. 2001;  16 260-266
• 24 Vesely D L, Maldonodo A, Levey G S. Partial hypopituitarism and possible hypothalamic involvement in sarcoidosis: report of a case and review of the literature.  Am J Med. 1977;  62 425-431
• 25 Guoth M S, Kim J, de Lotbiniere A C, Brines M L. Neurosarcoidosis presenting as hypopituitarism and a cystic pituitary mass.  Am J Med Sci. 1998;  315 220-224
• 26 Vesely D L. Hypothalamic sarcoidosis: a new cause of morbid obesity.  South Med J. 1989;  82 758-761
• 27 Colover J. Sarcoidosis with involvement of the nervous system.  Brain. 1948;  71(Pt. 4) 451-475
• 28 Jefferson M. Sarcoidosis of the nervous system.  Brain. 1957;  80 540-556
• 29 Krumholz A, Stern B J, Stern E G. Clinical implications of seizures in neurosarcoidosis.  Arch Neurol. 1991;  48 842-844
• 30 Hodge M H, Williams R L, Fukui M B. Neurosarcoidosis presenting as acute infarction on diffusion-weighted MR imaging: summary of radiologic findings.  AJNR Am J Neuroradiol. 2007;  28 84-86
• 31 Urich H. Neurosarcoidosis or granulomatous angiitis: a problem of definition.  Mt Sinai J Med. 1977;  44 718-725
• 32 Habersberger J, Manins V, Taylor A J. Cardiac sarcoidosis.  Intern Med J. 2008;  38 270-277
• 33 Joseph F G, Scolding N J. Sarcoidosis of the nervous system.  Pract Neurol. 2007;  7 234-244
• 34 Cox C E, Donohue J F, Brown C D, Kataria Y P, Judson M A. Health-related quality of life of persons with sarcoidosis.  Chest. 2004;  125 997-1004
• 35 Hayashi T, Onodera J, Nagata T, Mochizuki H, Itoyama Y. A case of biopsy-proven sarcoid meningoencephalitis presented with hallucination, nominal aphasia and dementia [in Japanese].  Rinsho Shinkeigaku. 1995;  35 1008-1011
• 36 Bona J R, Fackler S M, Fendley M J, Nemeroff C B. Neurosarcoidosis as a cause of refractory psychosis: a complicated case report.  Am J Psychiatry. 1998;  155 1106-1108
• 37 O’Brien G M, Baughman R P, Broderick J P, Arnold L, Lower E E. Paranoid psychosis due to neurosarcoidosis.  Sarcoidosis. 1994;  11 34-36
• 38 Willigers H, Koehler P J. Amnesic syndrome caused by neurosarcoidosis.  Clin Neurol Neurosurg. 1993;  95 131-135
• 39 Friedman S H, Gould D J. Neurosarcoidosis presenting as psychosis and dementia: a case report.  Int J Psychiatry Med. 2002;  32 401-403
• 40 Koffman B, Junck L, Elias S B, Feit H W, Levine S R. Polyradiculopathy in sarcoidosis.  Muscle Nerve. 1999;  22 608-613
• 41 Miller R, Sheron N, Semple S. Sarcoidosis presenting with an acute Guillain-Barré syndrome.  Postgrad Med J. 1989;  65 765-767
• 42 Nemni R, Galassi G, Cohen M et al.. Symmetric sarcoid polyneuropathy: analysis of a sural nerve biopsy.  Neurology. 1981;  31 1217-1223
• 43 Jamal M M, Cilursu A M, Hoffman E L. Sarcoidosis presenting as acute myositis. Report and review of the literature.  J Rheumatol. 1988;  15 1868-1871
• 44 Silverstein A, Siltzbach L E. Muscle involvement in sarcoidosis: asymptomatic, myositis, and myopathy.  Arch Neurol. 1969;  21 235-241
• 45 Pickuth D, Heywang-Köbrunner S H. Neurosarcoidosis: evaluation with MRI.  J Neuroradiol. 2000;  27 185-188
• 46 Pickuth D, Spielmann R P, Heywang-Köbrunner S H. Role of radiology in the diagnosis of neurosarcoidosis.  Eur Radiol. 2000;  10 941-944
• 47 Lury K M, Smith J K, Matheus M G, Castillo M. Neurosarcoidosis—review of imaging findings.  Semin Roentgenol. 2004;  39 495-504
• 48 Hayes W S, Sherman J L, Stern B J, Citrin C M, Pulaski P DMR. MR and CT evaluation of intracranial sarcoidosis.  AJR Am J Roentgenol. 1987;  149 1043-1049
• 49 Uzawa A, Kojima S, Yonezu T, Kanesaka T. Truncal polyradiculopathy due to sarcoidosis.  J Neurol Sci. 2009;  281 108-109
• 50 Fahoum F, Drory V E, Issakov J, Neufeld M Y. Neurosarcoidosis presenting as Guillain-Barré-like syndrome: a case report and review of the literature.  J Clin Neuromuscul Dis. 2009;  11 35-43
• 51 Uruha A, Koide R, Taniguchi M. Unusual presentation of sarcoidosis: solitary intracranial mass lesion mimicking a glioma.  J Neuroimaging. 2009 August 7;  , [Epub ahead of print]
• 52 Shah R, Roberson G H, Curé J K. Correlation of MR imaging findings and clinical manifestations in neurosarcoidosis.  AJNR Am J Neuroradiol. 2009;  30 953-961
• 53 Rodriguez F, Link M J, Driscoll C L, Giannini C. Neurosarcoidosis mimicking meningioma.  Arch Neurol. 2005;  62 148-149
• 54 Ng D, Jacobs M, Mantil J. Combined C-11 methionine and F-18 FDG PET imaging in a case of neurosarcoidosis.  Clin Nucl Med. 2006;  31 373-375
• 55 Aide N, Benayoun M, Kerrou K, Khalil A, Cadranel J, Talbot J N. Impact of [18F]-fluorodeoxyglucose ([18F]-FDG) imaging in sarcoidosis: unsuspected neurosarcoidosis discovered by [18F]-FDG PET and early metabolic response to corticosteroid therapy.  Br J Radiol. 2007;  80 e67-e71
• 56 Khoury J, Wellik K E, Demaerschalk B M, Wingerchuk D M. Cerebrospinal fluid angiotensin-converting enzyme for diagnosis of central nervous system sarcoidosis.  Neurologist. 2009;  15 108-111
• 57 Tahmoush A J, Amir M S, Connor W W et al.. CSF-ACE activity in probable CNS neurosarcoidosis.  Sarcoidosis Vasc Diffuse Lung Dis. 2002;  19 191-197
• 58 Moravan M, Segal B M. Treatment of CNS sarcoidosis with infliximab and mycophenolate mofetil.  Neurology. 2009;  72 337-340
• 59 Vucinic V M. What is the future of methotrexate in sarcoidosis? A study and review.  Curr Opin Pulm Med. 2002;  8 470-476
• 60 Doty J D, Mazur J E, Judson M A. Treatment of corticosteroid-resistant neurosarcoidosis with a short-course cyclophosphamide regimen.  Chest. 2003;  124 2023-2026
• 61 Sharma O P. Effectiveness of chloroquine and hydroxychloroquine in treating selected patients with sarcoidosis with neurological involvement.  Arch Neurol. 1998;  55 1248-1254
• 62 Sodhi M, Pearson K, White E S, Culver D A. Infliximab therapy rescues cyclophosphamide failure in severe central nervous system sarcoidosis.  Respir Med. 2009;  103 268-273
• 63 Santos E, Shaunak S, Renowden S A, Scolding N J. Treatment of refractory neurosarcoidosis with infliximab.  J Neurol Neurosurg Psychiatry. 2010;  81 241-246
• 64 Carter J D, Valeriano J, Vasey F B, Bognar B. Refractory neurosarcoidosis: a dramatic response to infliximab.  Am J Med. 2004;  117 277-279
• 65 Bruns F, Pruemer B, Haverkamp U, Fischedick A R. Neurosarcoidosis: an unusual indication for radiotherapy.  Br J Radiol. 2004;  77 777-779