Neurosarcoidosis. Difficulties of diagnosis

Objective: to present a clinical case of neurosarcoidosis demonstrating the difficulties in diagnosing this disease and to discuss the features of its clinical manifestations, diagnosis, and treatment.
Materials and Methods. A clinical case of a 28-year-old patient with neurosarcoidosis is described. The diagnostic process included clinical examination, laboratory tests, neuroimaging (CT and MRI of the brain), lymph node biopsy with histological and immunohistochemical examination, and autopsy.
Results. The patient presented with symptoms such as severe headache, disorientation, anisocoria, sensory impairment, epileptic seizures, and psychomotor agitation. Brain MRI revealed leptomeningeal enhancement of the contrast agent. Lymph node biopsy confirmed granulomatous lymphadenitis characteristic of sarcoidosis. Despite the recommended glucocorticoid therapy, the disease progressed, and the patient died due to cerebellar infarction and cerebral edema. Autopsy verified sarcoidosis with involvement of the leptomeninges, spleen, and lymph nodes.
Conclusions. Neurosarcoidosis is a rare disease with diverse clinical manifestations, making timely diagnosis challenging. A comprehensive approach, including clinical examination, neuroimaging, histological examination, and exclusion of other diseases, is crucial for establishing the diagnosis. Timely initiation of immunosuppressive therapy may improve the prognosis of the disease.

1. Ramazanov G.R., Kokov L.S., Kovaleva E.A., Korigova H.V., Parkhomenko M.V., Petrikov S.S. Thrombectomy in patients with basilar artery thrombosis and decreased level of wakefulness (Clinical observation). Journal of Diagnostic and Interventional Radiology. 2021;15(2);55-64. (In Russ). https://doi.org/10.25512/DIR.2021.15.2.06

2. Fernandes PM, Whiteley WN, Hart SR, et al. Strokes: mimics and chameleons. Pract Neurol. 2013;13:21–8. https://doi.org/10.1136/practneurol2012-000465

3. Gibson LM, Whiteley W. The differential diagnosis of suspected stroke: a systematic review. J R Coll Physicians Edinb 2013;43:114–18. https://doi.org/10.4997/JRCPE.2013.205

4. Valtonen VV. Infection as a risk factor for infarction and atherosclerosis. Ann Med. 1991;23:539–43.

5. Tentschert S, Wimmer R, Greisenegger S, et al. Headache at stroke onset in 2196 patients with ischaemic stroke or transient ischaemic attack. Stroke. 2005;36:e1–3.

6. Morgenstern LB, Frankowski RF. Brain tumor masquerading as stroke. J Neurooncol. 1999;44:47–52.

7. Ramazanov G.R., Kovaleva E.A., Stepanov V.N., Korigova H.V., Shevchenko E.V., Zabrodskaya Y.V., Petrikov S.S. Clinical Cases of Wernicke Encephalopathy. Russian Sklifosovsky Journal "Emergency Medical Care". 2020;9(2):292-297. (In Russ). https://doi.org/10.23934/2223-9022-2020-9-2-292-297

8. Shevchenko E.V., Ramazanov G.R., Petrikov S.S. Сauses of Dizziness in Patients with Suspected Stroke. Russian Sklifosovsky Journal "Emergency Medical Care". 2018;7(3):217-221. (In Russ). https://doi.org/10.23934/2223-9022-2018-7-3-217-221

9. Gerke AK. Morbidity and mortality in sarcoidosis. Curr Opin Pulm Med. 2014 Sep;20(5):472-8. https://doi.org/10.1097/MCP.0000000000000080 PMID: 25029298; PMCID: PMC4326053.

10. Ramazanov G.R., Shevchenko E.V., Idilova L.I., Stepanov V.N., Nugaeva E.V., Petrikov S.S. Neurosarcoidosis. Russian neurological journal. 2020;25(5):45-50. (In Russ). https://doi.org/10.30629/2658-7947-2020-25-5-45-50 https://www.r-n-j.com/jour/article/view/121/78

11. Kidd D.P. Neurosarcoidosis: Clinical Manifestations, Investigation and Treatment. Pract. Neurol. 2020;20:199–212. https://doi.org/10.1136/practneurol-2019-002349 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066110/

12. Cação G., Branco A., Meireles M., Alves J.E., Mateus A., Silva A.M., Santos E. Neurosarcoidosis According to Zajicek and Scolding Criteria: 15 Probable and Definite Cases, Their Treatment and Outcomes. J. Neurol. Sci. 2017;379:84–88. https://doi.org/10.1016/j.jns.2017.05.055 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066110/

13. Schupp J.C., Freitag-Wolf S., Bargagli E., Mihailović-Vučinić V., Rottoli P., Grubanovic A., Müller A., Jochens A., Tittmann L., Schnerch J., et al. Phenotypes of Organ Involvement in Sarcoidosis. Eur. Respir. J. 2018;51:1700991. https://doi.org/10.1183/13993003.00991-2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066110/

14. Scott TF, Yandora K, Valeri A, Chieffe C, Schramke C. Aggressive therapy for neurosarcoidosis: long-term follow-up of 48 treated patients. Arch Neurol. 2007;64(5):691-696.

15. Krumholz A, Stern BJ. Neurologic manifestations of sarcoidosis. Handb Clin Neurol. 2014; 119:305-333. Schupp J.C., Freitag-Wolf S., Bargagli E., Mihailović-Vučinić V., Rottoli P., Grubanovic A., Müller A., Jochens A., Tittmann L., Schnerch J., et al. Phenotypes of Organ Involvement in Sarcoidosis. Eur. Respir. J. 2018;51:1700991. https://doi.org/10.1183/13993003.00991-2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066110/

16. Kellinghaus C., Schilling M., Ludemann P. Neurosarcoidosis: Clinical experience and diagnostic pitfalls. Eur. Neurol. 2004;51:84–88. https://doi.org/10.1159/000076534

17. Culver D.A., Neto M.L.R., Moss B.P., Willis M.A. Neurosarcoidosis. Semin. Respir. Crit. Care Med. 2017;38:499–513. https://doi.org/10.1055/s-0037-1604165

18. Kellinghaus C., Schilling M., Ludemann P. Neurosarcoidosis: Clinical experience and diagnostic pitfalls. Eur. Neurol. 2004;51:84–88. https://doi.org/10.1159/000076534.

19. Bradshaw MJ, Pawate S, Koth LL, Cho TA, Gelfand JM. Neurosarcoidosis: Pathophysiology, Diagnosis, and Treatment. Neurol Neuroimmunol Neuroinflamm. 2021 Oct 4;8(6):e1084. https://doi.org/10.1212/NXI.0000000000001084 PMID: 34607912; PMCID: PMC8495503.

20. Pawate S, Moses H, Sriram S. Presentations and outcomes of neurosarcoidosis: a study of 54 cases. QJM. 2009;102(7):449-460.

21. Carlson ML, White JR Jr., Espahbodi M, et al.. Cranial base manifestations of neurosarcoidosis: a review of 305 patients. Otol Neurotol. 2015;36(1):156-166.

22. Zamora C, Hung SC, Tomingas C, Atkinson C, Castillo M. Engorgement of deep medullary veins in neurosarcoidosis: a common-yetunderrecognized cerebrovascular finding on SWI. AJNR Am J Neuroradiol. 2018;39 (11):2045-2050.

23. Bridel C, Courvoisier DS, Vuilleumier N, Lalive PH. Cerebrospinal fluid angiotensin-converting enzyme for diagnosis of neurosarcoidosis. J Neuroimmunol. 2015;285:1-3.

24. Rao PB, Azim A, Singh N, Baronia AK, Kumar A, Poddar B. Osmotic demyelination syndrome in Intensive Care Unit. Indian J Crit Care Med. 2015;19:166–169.

25. Саркоидоз: монография / Под ред. Визеля А.А. (Серия монографийРоссийского респираторного общества; Гл. ред. серии Чучалин А.Г.). М.: Издательский холдинг «Атмосфера», 2010. 416 с. https://spulmo.ru/upload/kr/Sarkoidoz_2022.pdf

26. James W.E., Baughman R. Treatment of sarcoidosis: grading the evidence. Expert Rev Clin Pharmacol. 2018 Jul;11(7):677-687. https://doi.org/10.1080/17512433.2018.1486706

27. Deverrière G., Flamans-Klein A., Firmin D., Azouzi O., Courville P., Le Roux P. Early onset pediatric sarcoidosis, diagnostic problems. Arch Pediatr. 2012 Jul;19(7):707-10. https://doi.org/10.1016/j.arcped.2012.04.024

28. Joubert B, Chapelon-Abric C, Biard L, et al. Association of prognostic factors and immunosuppressive treatment with long-term outcomes in neurosarcoidosis. JAMA Neurol. 2017;74(11):1336-1344.

29. Sakkat, A., Cox, G., Khalidi, N. et al. Infliximab therapy in refractory sarcoidosis: a multicenter real-world analysis. Respir Res. 2022;54. https://doi.org/10.1186/s12931-022-01971-5