Ognerubov NA, Mirsalimova OO, Zemur MA. Paraneoplastic limbic encephalitis in a patient with small cell lung cancer. Case report. Consilium Medicum. 2024;26(12):879–885. DOI: 10.26442/20751753.2024.12.203050
Паранеопластический лимбический энцефалит при мелкоклеточном раке легких: клинический случай
Огнерубов Н.А., Мирсалимова О.О., Земур М.А. Паранеопластический лимбический энцефалит при мелкоклеточном раке легких: клинический случай. Consilium Medicum. 2024;26(12):879–885. DOI: 10.26442/20751753.2024.12.203050
Ognerubov NA, Mirsalimova OO, Zemur MA. Paraneoplastic limbic encephalitis in a patient with small cell lung cancer. Case report. Consilium Medicum. 2024;26(12):879–885. DOI: 10.26442/20751753.2024.12.203050
Паранеопластический лимбический энцефалит (ПЛЭ) является редким аутоиммунным неврологическим синдромом, обусловленным избирательным поражением лимбической системы с развитием нейропсихиатрических симптомов и когнитивных нарушений, ассоциирован со злокачественной опухолью. Мы наблюдали ПЛЭ у больного с мелкоклеточным раком легкого (МКРЛ). Пациент Б. обратился с жалобами на сильную слабость, приступы головной боли, раздражительность, снижение памяти, судороги в мышцах конечностей на протяжении 2 мес. По данным магнитно-резонансной томографии головного мозга с контрастированием обнаружены признаки ЛЭ. В сыворотке крови выявлены антинейрональные антитела: анти-Hu, анти-CV2, анти-Ма2, анти-амфифизин. В ликворе обнаружены анти-Hu, лимфоцитоз 88% и повышение белка до 0,6 г/л. Пациент консультирован неврологом, диагностирован ПЛЭ. Лечение не проводилось. Через 2 мес больной отметил значительное ухудшение. Нарушение памяти прогрессировало, судорожные припадки с кратковременной потерей сознания участились, стал агрессивным, замкнутым. Произведена позитронно-эмиссионная томография, совмещенная с компьютерной томографией с 18F-фтордезоксиглюкозой. Отмечалась гиперэкспрессия радиофармпрепарата в медиальных отделах левой височной доли на ограниченном участке. В верхней доле правого легкого выявлена опухоль. Сделана бронхоскопия с биопсией. При гистологическом исследовании – МКРЛ. Клинический диагноз «Мелкоклеточный рак правого легкого стадия IIb cT2bN1M0. ПЛЭ». Назначена цитотоксическая и иммунотерапия. Случай свидетельствует, что ПЛЭ является редким неврологическим синдромом, связанным в большинстве случаев с МКРЛ, как правило, на ранних стадиях опухолевого процесса. Нейропсихиатрические и когнитивные нарушения и судороги являются преобладающими в клинической практике. Нейровизуализация ПЛЭ осуществляется на магнитно-резонансной томографии с контрастированием и позитронно-эмиссионной томографии, совмещенной с компьютерной томографией с 18F-фтордезоксиглюкозой, последняя является методом выбора. Аутоиммунный (паранеопластический) характер процесса подтверждается наличием антинейрональных антител в сыворотке крови и ликворе.
Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome caused by selective involvement of the limbic system with the development of neuropsychiatric symptoms and cognitive impairment. PLE is associated with malignancies. We observed PLE in a patient with small cell lung cancer (SCLC). Patient B. complained of severe weakness, headache attacks, irritability, memory loss, and cramps in the muscles of the limbs for 2 months. Contrast-enhanced magnetic resonance imaging of the brain showed signs of PLE. Anti-neuronal antibodies were detected in the blood serum: anti-Hu, anti-CV2 and anti-Ma2, anti-amphiphysin. In the cerebrospinal fluid, anti-Hu antibodies, lymphocytosis of 88%, and increased protein of 0.6 g/L were found. The patient was consulted by a neurologist and diagnosed with PLE. No treatment was administered. After 2 months, the patient reported a significant deterioration. Memory impairment progressed, convulsive seizures with short-term loss of consciousness became more frequent, and the patient became aggressive and withdrawn. Positron emission tomography combined with computed tomography with 18F-fluorodeoxyglucose was performed. There was an excessive radiopharmaceutical uptake in a limited area of the medial parts of the left temporal lobe. A tumor was detected in the upper lobe of the right lung. A bronchoscopy with biopsy was performed. Histological examination showed SCLC. Clinical diagnosis: SCLC of the right lung, stage IIb cT2bN1M0; PLE. Cytotoxic and immunotherapy were administered. The case shows that PLE is a rare neurological syndrome associated in most cases with SCLC, usually in the early stages of the malignancy. Neuropsychiatric and cognitive disorders and seizures are predominant in clinical presentation. PLE neuroimaging is performed using contrast-enhanced magnetic resonance imaging and positron emission tomography combined with computed tomography with 18F-fluorodeoxyglucose, the latter being the method of choice. The presence of antineuronal antibodies in serum and cerebrospinal fluid confirms the autoimmune (paraneoplastic) nature of the process.
1. Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today (version 1.1). Lyon, France: International Agency for Research on Cancer. 2024. Available at: https://gco.iarc.who.int/today. Accessed: 11.10.2024.
2. Shen K, Xu Y, Guan H, et al. Paraneoplastic limbic encephalitis associated with lung cancer. Sci Rep. 2018;8(1):6792. DOI:10.1038/s41598-018-25294-y
3. Darnell RB, Posner JB. Paraneoplastic syndromes affecting the nervous system. Semin Oncol. 2006;33(3):270-98. DOI:10.1053/j.seminoncol.2006.03.008
4. Collao-Parra JP, Romero-Urra C, Delgado-Derio C. Autoimmune encephalitis. A review. Rev Med Chil. 2018;146(3):351-61 (in Spanish). DOI:10.4067/s0034-98872018000300351
5. Altabakhi IW, Babiker HM, Lui F. Paraneoplastic Limbic Encephalitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024. PMID: 30137808. Available at: https://www.ncbi.nlm.nih.gov/books/NBK519523/ Accessed: 10.10.2024.
6. Said S, Cooper CJ, Reyna E, et al. Paraneoplastic limbic encephalitis, an uncommon presentation of a common cancer: Case report and discussion. Am J Case Rep. 2013;14:391-4. DOI:10.12659/AJCR.889560
7. Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. 2005;128(Pt. 8):1764-77. DOI:10.1093/brain/awh526
8. Corsellis JA, Goldberg GJ, Norton AR. "Limbic encephalitis" and its association with carcinoma. Brain. 1968;91(3):481-96. DOI:10.1093/brain/91.3.481
9. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000;123(Pt. 7):1481-94. DOI:10.1093/brain/123.7.1481
10. Rosenfeld MR, Dalmau J. Cancer and the Nervous System. Paraneoplastic Disorders of the Nervous System. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, eds. Neurology in clinical practice. 5th ed. Butterworth-Heinemann, Elsevier, 2008; р.1405-15.
11. Торопина Г.Г., Яхно Н.Н., Воскресенская О.Н., и др. Лимбический энцефалит. Обзор литературы и клинические наблюдения. Неврологический журнал. 2013;18(3):11-21 [Toropina GG, Yakhno NN, Voskresenskaya ON, et al. Limbic encephalitis. Literature review and case reports. Nevrologicheskii Zhurnal. 2013;18(3):11-21 (in Russian)].
12. Inuzuka T. Paraneoplastic neurological syndrome–definition and history. Brain Nerve. 2010;62(4):301-8 (in Japanese).
13. Gozzard P, Woodhall M, Chapman C, et al. Paraneoplastic neurologic disorders in small cell lung carcinoma: A prospective study. Neurology. 2015;85(3):235-9. DOI:10.1212/WNL.0000000000001721
14. Scheid R, Honnorat J, Delmont E, et al. A new anti-neuronal antibody in a case of paraneoplastic limbic encephalitis associated with breast cancer. J Neurol Neurosurg Psychiatry. 2004;75:338-40.
15. Tüzün E, Dalmau J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist. 2007;13(5):261-71. DOI:10.1097/NRL.0b013e31813e34a5
16. Dalmau J, Bataller L. Clinical and immunological diversity of limbic encephalitis: a model for paraneoplastic neurologic disorders. Hematol Oncol Clin North Am. 2006;20:1319-35. DOI:10.1016/j.hoc.2006.09.011
17. Dalmau J, Graus F. Antibody-Mediated Encephalitis. N Engl J Med. 2018;378(9):840-51. DOI:10.1056/NEJMra1708712
18. Dalmau J, Geis C, Graus F. Autoantibodies to Synaptic Receptors and Neuronal Cell Surface Proteins in Autoimmune Diseases of the Central Nervous System. Physiol Rev. 2017;97(2):839-87. DOI:10.1152/physrev.00010.2016
19. Rees JH. Paraneoplastic syndromes: when to suspect, how to confirm, and how to manage. J Neurol Neurosurg Psychiatry. 2004;75(Suppl. 2):ii43-50. DOI:10.1136/jnnp.2004.040378
20. Dalmau J, Lancaster E, Martinez-Hernandez E, et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10:63-74. DOI:10.1016/S1474-4422(10)70253-2
21. Pollak TA, Lennox BR, Müller S, et al. Autoimmune psychosis: an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatry. 2020;7(1):93-108. DOI:10.1016/S2215-0366(19)30290-1. Erratum in: Lancet Psychiatry. 2019;6(12):e31. DOI:10.1016/S2215-0366(19)30439-0
22. Nathoo N, Anderson D, Jirsch J. Extreme Delta Brush in Anti-NMDAR Encephalitis Correlates With Poor Functional Outcome and Death. Front Neurol. 2021;12:686521. DOI:10.3389/fneur.2021.686521
23. Graus F, Keime-Guibert F, Reñe R, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain. 2001;124(Pt. 6):1138-48. DOI:10.1093/brain/124.6.1138
24. Kelley BP, Patel SC, Marin HL, et al. Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis. AJNR Am J Neuroradiol. 2017;38(6):1070-8. DOI:10.3174/ajnr.A5086
25. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004;75(8):1135-40. DOI:10.1136/jnnp.2003.034447
26. Funaguchi N, Ohno Y, Endo J, et al. [Paraneoplastic neurological syndrome accompanied by severe central hypoventilation and expression of anti-Hu antibody in a patient with small cell lung cancer]. Nihon Kokyuki Gakkai Zasshi. 2008;46(4):314-8 [Article in Japanese].
27. Ando T, Goto Y, Mano K, et al. Paraneoplastic autoimmune encephalitis associated with pleomorphic lung carcinoma: An autopsy case report. Neuropathology. 2018. DOI:10.1111/neup.12477
28. Höftberger R, Lassmann H. Immune-mediated disorders. Handb Clin Neurol. 2017;145:285-99. DOI:10.1016/B978-0-12-802395-2.00020-1
29. Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol. 2008;7(4):327-40. DOI:10.1016/S1474-4422(08)70060-7
30. Lawn ND, Westmoreland BF, Kiely MJ, et al. Clinical, magnetic resonance imaging, and electroencephalographic findings in paraneoplastic limbic encephalitis. Mayo Clin Proc. 2003;78(11):1363-8. DOI:10.4065/78.11.1363
31. Graus F, Vogrig A, Muñiz-Castrillo S, et al. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(4):e1014. DOI:10.1212/NXI.0000000000001014
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33. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404. DOI:10.1016/S1474-4422(15)00401-9
34. Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro Oncol. 2014;16(6):771–8. DOI:10.1093/neuonc/nou030
35. Urbach H, Soeder BM, Jeub M, et al. Serial MRI of limbic encephalitis. Neuroradiology. 2006;48(6):380-6. DOI:10.1007/s00234-006-0069-0
36. Heine J, Prüss H, Bartsch T, et al. Imaging of autoimmune encephalitis – Relevance for clinical practice and hippocampal function. Neuroscience. 2015;309:68-83. DOI:10.1016/j.neuroscience.2015.05.037
37. Younes-Mhenni S, Janier MF, Cinotti L, et al. FDG-PET improves tumour detection in patients with paraneoplastic neurological syndromes. Brain. 2004;127(Pt. 10):2331-8. DOI:10.1093/brain/awh247
38. Chanson JB, Diaconu M, Honnorat J, et al. PET follow-up in a case of anti-NMDAR encephalitis: arguments for cingulate limbic encephalitis. Epileptic Disord. 2012;14(1):90-3. DOI:10.1684/epd.2012.0486
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________________________________________________
1. Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today (version 1.1). Lyon, France: International Agency for Research on Cancer. 2024. Available at: https://gco.iarc.who.int/today. Accessed: 11.10.2024.
2. Shen K, Xu Y, Guan H, et al. Paraneoplastic limbic encephalitis associated with lung cancer. Sci Rep. 2018;8(1):6792. DOI:10.1038/s41598-018-25294-y
3. Darnell RB, Posner JB. Paraneoplastic syndromes affecting the nervous system. Semin Oncol. 2006;33(3):270-98. DOI:10.1053/j.seminoncol.2006.03.008
4. Collao-Parra JP, Romero-Urra C, Delgado-Derio C. Autoimmune encephalitis. A review. Rev Med Chil. 2018;146(3):351-61 (in Spanish). DOI:10.4067/s0034-98872018000300351
5. Altabakhi IW, Babiker HM, Lui F. Paraneoplastic Limbic Encephalitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2024. PMID: 30137808. Available at: https://www.ncbi.nlm.nih.gov/books/NBK519523/ Accessed: 10.10.2024.
6. Said S, Cooper CJ, Reyna E, et al. Paraneoplastic limbic encephalitis, an uncommon presentation of a common cancer: Case report and discussion. Am J Case Rep. 2013;14:391-4. DOI:10.12659/AJCR.889560
7. Ances BM, Vitaliani R, Taylor RA, et al. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. Brain. 2005;128(Pt. 8):1764-77. DOI:10.1093/brain/awh526
8. Corsellis JA, Goldberg GJ, Norton AR. "Limbic encephalitis" and its association with carcinoma. Brain. 1968;91(3):481-96. DOI:10.1093/brain/91.3.481
9. Gultekin SH, Rosenfeld MR, Voltz R, et al. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000;123(Pt. 7):1481-94. DOI:10.1093/brain/123.7.1481
10. Rosenfeld MR, Dalmau J. Cancer and the Nervous System. Paraneoplastic Disorders of the Nervous System. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, eds. Neurology in clinical practice. 5th ed. Butterworth-Heinemann, Elsevier, 2008; р.1405-15.
11. Toropina GG, Yakhno NN, Voskresenskaya ON, et al. Limbic encephalitis. Literature review and case reports. Nevrologicheskii Zhurnal. 2013;18(3):11-21 (in Russian).
12. Inuzuka T. Paraneoplastic neurological syndrome–definition and history. Brain Nerve. 2010;62(4):301-8 (in Japanese).
13. Gozzard P, Woodhall M, Chapman C, et al. Paraneoplastic neurologic disorders in small cell lung carcinoma: A prospective study. Neurology. 2015;85(3):235-9. DOI:10.1212/WNL.0000000000001721
14. Scheid R, Honnorat J, Delmont E, et al. A new anti-neuronal antibody in a case of paraneoplastic limbic encephalitis associated with breast cancer. J Neurol Neurosurg Psychiatry. 2004;75:338-40.
15. Tüzün E, Dalmau J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist. 2007;13(5):261-71. DOI:10.1097/NRL.0b013e31813e34a5
16. Dalmau J, Bataller L. Clinical and immunological diversity of limbic encephalitis: a model for paraneoplastic neurologic disorders. Hematol Oncol Clin North Am. 2006;20:1319-35. DOI:10.1016/j.hoc.2006.09.011
17. Dalmau J, Graus F. Antibody-Mediated Encephalitis. N Engl J Med. 2018;378(9):840-51. DOI:10.1056/NEJMra1708712
18. Dalmau J, Geis C, Graus F. Autoantibodies to Synaptic Receptors and Neuronal Cell Surface Proteins in Autoimmune Diseases of the Central Nervous System. Physiol Rev. 2017;97(2):839-87. DOI:10.1152/physrev.00010.2016
19. Rees JH. Paraneoplastic syndromes: when to suspect, how to confirm, and how to manage. J Neurol Neurosurg Psychiatry. 2004;75(Suppl. 2):ii43-50. DOI:10.1136/jnnp.2004.040378
20. Dalmau J, Lancaster E, Martinez-Hernandez E, et al. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol. 2011;10:63-74. DOI:10.1016/S1474-4422(10)70253-2
21. Pollak TA, Lennox BR, Müller S, et al. Autoimmune psychosis: an international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatry. 2020;7(1):93-108. DOI:10.1016/S2215-0366(19)30290-1. Erratum in: Lancet Psychiatry. 2019;6(12):e31. DOI:10.1016/S2215-0366(19)30439-0
22. Nathoo N, Anderson D, Jirsch J. Extreme Delta Brush in Anti-NMDAR Encephalitis Correlates With Poor Functional Outcome and Death. Front Neurol. 2021;12:686521. DOI:10.3389/fneur.2021.686521
23. Graus F, Keime-Guibert F, Reñe R, et al. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain. 2001;124(Pt. 6):1138-48. DOI:10.1093/brain/124.6.1138
24. Kelley BP, Patel SC, Marin HL, et al. Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis. AJNR Am J Neuroradiol. 2017;38(6):1070-8. DOI:10.3174/ajnr.A5086
25. Graus F, Delattre JY, Antoine JC, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004;75(8):1135-40. DOI:10.1136/jnnp.2003.034447
26. Funaguchi N, Ohno Y, Endo J, et al. [Paraneoplastic neurological syndrome accompanied by severe central hypoventilation and expression of anti-Hu antibody in a patient with small cell lung cancer]. Nihon Kokyuki Gakkai Zasshi. 2008;46(4):314-8 [Article in Japanese].
27. Ando T, Goto Y, Mano K, et al. Paraneoplastic autoimmune encephalitis associated with pleomorphic lung carcinoma: An autopsy case report. Neuropathology. 2018. DOI:10.1111/neup.12477
28. Höftberger R, Lassmann H. Immune-mediated disorders. Handb Clin Neurol. 2017;145:285-99. DOI:10.1016/B978-0-12-802395-2.00020-1
29. Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol. 2008;7(4):327-40. DOI:10.1016/S1474-4422(08)70060-7
30. Lawn ND, Westmoreland BF, Kiely MJ, et al. Clinical, magnetic resonance imaging, and electroencephalographic findings in paraneoplastic limbic encephalitis. Mayo Clin Proc. 2003;78(11):1363-8. DOI:10.4065/78.11.1363
31. Graus F, Vogrig A, Muñiz-Castrillo S, et al. Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(4):e1014. DOI:10.1212/NXI.0000000000001014
32. Shnayder NA, Dmitrenko DV, Dykhno YuA, Ezhikova VV. Paraneoplastic limbic encephalitis in neuorological and oncological practice. Rossiiskii Onkologicheskii Zhurnal.
2013;(1):49-57 (in Russian).
33. Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404. DOI:10.1016/S1474-4422(15)00401-9
34. Dalmau J, Rosenfeld MR. Autoimmune encephalitis update. Neuro Oncol. 2014;16(6):771–8. DOI:10.1093/neuonc/nou030
35. Urbach H, Soeder BM, Jeub M, et al. Serial MRI of limbic encephalitis. Neuroradiology. 2006;48(6):380-6. DOI:10.1007/s00234-006-0069-0
36. Heine J, Prüss H, Bartsch T, et al. Imaging of autoimmune encephalitis – Relevance for clinical practice and hippocampal function. Neuroscience. 2015;309:68-83. DOI:10.1016/j.neuroscience.2015.05.037
37. Younes-Mhenni S, Janier MF, Cinotti L, et al. FDG-PET improves tumour detection in patients with paraneoplastic neurological syndromes. Brain. 2004;127(Pt. 10):2331-8. DOI:10.1093/brain/awh247
38. Chanson JB, Diaconu M, Honnorat J, et al. PET follow-up in a case of anti-NMDAR encephalitis: arguments for cingulate limbic encephalitis. Epileptic Disord. 2012;14(1):90-3. DOI:10.1684/epd.2012.0486
39. Philippov PP. Paraneoplastic antigens and early diagnostics of cancer. Soros Educational Journal. 2000;6(9): 25-30 (in Russian).
Авторы
Н.А. Огнерубов*1, О.О. Мирсалимова2, М.А. Земур3
1ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия; 2Федеральная сеть центров ядерной медицины «ПЭТ-Технолоджи», Москва, Россия; 3Онкорадиологический центр «ПЭТ-Технолоджи», Подольск, Россия
*ognerubov_n.a@mail.ru
________________________________________________
Nikolai A. Ognerubov*1, Olga O. Mirsalimova2, Mikhail A. Zemur3
1Russian Medical Academy of Continuous Professional Education, Moscow, Russia; 2Federal Network of Nuclear Medicine Centers “PET-Technology”, Moscow, Russia; 3PET-Technology Oncoradiology Center, Podolsk, Russia
*ognerubov_n.a@mail.ru