Abstract
Aim: Paraneoplastic neurological syndromes (PNS) refer to a group of syndromes generally mediated by immune responses triggered by the underlying tumor and cover different clinical spectrums that can affect every level in the nervous system. Therefore, it causes difficulties in diagnosis for patients. This study aimed to evaluate and discuss the clinical and laboratory characteristics and patient management of patients with PNS retrospectively.
Material and Methods: In this study, the data of patients with clinical findings compatible with PNS and antibody positivity who were followed up in the neurology outpatient clinic, neurology service or intensive care unit at Başkent University Ankara Hospital between 2012 and 2023 were evaluated retrospectively. Totally 342 patients with a preliminary diagnosis of were investigated. Demographic data, serum and cerebrospinal fluid results, brain magnetic resonance imaging examination results, electroencephalography and electromyography evaluations, types of treatment, treatment response and follow-up data were examined. Data were analyzed using the SPSS program.
Results: After the exclusion criteria, the data of a total of 21 patients were evaluated. 57.1% (n=12) of the patients were male and the mean age of the patients was 69.57 ± 11.18 years. Limbic encephalitis (n=6, 28.6%) and rapidly progressive cerebellar syndrome (n=6, 28.6%) were most frequently detected in patients. Anti-amphiphysin, CASPR2 and Yo antibodies were the most commonly detected antibodies. No malignancy was observed in 8 patients (38.1%) during admission, treatment and follow-up. Intravenous pulse steroid therapy and intravenous immunoglobulin therapy were the most frequently applied treatment methods. Death was observed in 5 patients (23.8%) during the follow-up period.
Conclusion: PNS is a rare syndrome that is difficult to diagnose and the patient is often misdiagnosed or the diagnosis may be missed. PNS related data from different centers are needed for early recognition of symptoms and determination of the appropriate diagnosis or treatment plan.
Keywords
Paraneoplastic neurological syndrome limbic encephalitis onconeural antibody cerebellar syndrome
References
- 1. Devine MF, Kothapalli N, Elkhooly M, Dubey D. Paraneoplastic neurological syndromes: clinical presentations and management. Ther Adv Neuro Disord. 2021; 14:1756286420985323.
- 2. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis. 2007; 2:22.
- 3. Li L, Guo Y, Wang J. Detection of paraneoplastic antibodies and their significance in paraneoplastic neurologic syndromes: a narrative review. Ann Transl Med. 2023; 11(7):283.
- 4. Graber JJ. Paraneoplastic Neurologic Syndromes. Continuum (Minneap Minn). 2023;29(6):1779-1808
- 5. Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology. 1985, 35(4):538-43.
- 6. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004; 75(8):1135-40.
- 7. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000; 123 (Pt 7):1481-94.
- 8. Graus F, Vogrig A, Muniz-Castrillo S, Antoine JCG, Desestret V, Dubey D, et al. Updated diagnostic criteria for paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflamm. 2021; 8(4): e1014.
- 9. Höftberger R, Rosenfeld MR, Dalmau J. Update on neurological paraneoplastic syndromes. Curr Opin Oncol. 2015; 27(6):489-95.
- 10. Binks S, Uy C, Honnorat J, Irani SR. Paraneoplastic neurological syndromes: a practical approach to diagnosis and management. Pract Neurol. 2022; 22(1):19-31.
- 11. Giometto B, Grisold W, Vitaliani R, Graus F, Honnorat J, Bertolini G. Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers. Arch Neurol. 2010; 67(3):330-5.
- 12. Şen S, Terzi M. Paraneoplastic neurologic disorders. J Exp Clin Med. 2013; 30(3):209-13.
- 13. Oliveira V, Videira G, Samões R, Carneiro P, Neves E, Santos E. Paraneoplastic neurological syndromes with onconeural antibodies: a single center retrospective study. J Neurol Sci. 2020; 418:117103.
- 14. Boyko M, Au KLK, Casault C, de Robles P, Pfeffer G. Systematic review of the clinical spectrum of CASPR2 antibody syndrome. J Neurol. 2020; 267(4):1137-46.
- 15. Tüzün E, Bebek N, Sema İ, Durmuş H, Kürtüncü M, Gürses C, et al. Amphiphysin autoimmunity: associated neurological syndromes and tumors in the Turkish population. J Neurol Sci [Turk]. 2010;27(2):121- 6
- 16. Tüzün E, Dalmau J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist. 2007; 13(5):261-71.
- 17. Özözen Ayas Z, Kotan D, Oguz Akarsu E, Demiryürek BE. Analysis of the patients with autoimmune neurological syndromes in a single center in Turkey. Osmangazi Journal of Med. 2021; 43(1):62-9.
- 18. Erkoyun HU, Gündoğan S, Seçil Y, Beckmann Y, İncesu TK, Türe HS, et al. Paraneoplastic neurologic syndromes: rare but more common than expected nine cases with a literature review. Turk J Neurol. 2018; 24(1):63-9.
Abstract
Amaç: Paraneoplastik nörolojik sendromlar (PNS) genellikle altta yatan tümör tarafından tetiklenen immün yanıtların aracılık ettiği bir grup sendromu ifade etmekte olup, sinir sisteminde her düzeyi etkileyebilecek farklı klinik spektrumları kapsamaktadır. Bu nedenle hastalarda tanıda zorluklara neden olmaktadır. Bu çalışmada PNS ile değerlendirilen hastaların klinik ve laboraturar özelliklerinin ve hasta yönetimlerinin retrospektif olarak değerlendirilmesi ve tartışılması amaçlanmıştır.
Gereç ve Yöntemler: Bu çalışmada Başkent Üniversitesi Ankara Hastanesi’nde 2012-2023 yılları arasında nöroloji polikliniği, nöroloji servisi yada yoğun bakımda izlemi yapılmış PNS ile uyumlu klinik bulguları olan ve antikor pozitifliği saptanan hastaların verisi retrospektif olarak değerlendirilmiştir. PNS ön tanısı olan toplam 342 hasta verisi incelendi. Bireylerin demografik verileri, serum ve beyin omurilik sıvısı sonuçları, beyin manyetik rezonans görüntüleme tetkik sonuçları, elektroensefalografi ve elektromyografi değerlendirilmeleri, uygulanan tedavi türleri, taburculuk tedavi yanıtı ve takip verileri incelendi. Veriler SPSS programı kullanılarak analiz edildi.
Bulgular: Dışlama kriteri sonrasında toplam 21 hastanın verisi retrospektif olarak değerlendirildi. Hastaların %57.1’ i (n=12) erkek cinsiyetindeydi ve yaş ortalamaları 69.57 ± 11.18 yıldı. Hastalarda en sık limbik ensefalit (n=6, %28.6) ve hızlı progresif serebellar sendrom (n=6, %28.6) saptandı. Anti- amfifizin, CASPR2 ve Yo antikorları en sık saptanan antikorlardı. 8 hastada (%38.1) başvuru, tedavi ve takip süresince malignite izlenmedi. İntravenöz pulse steroid tedavisi ile intravenöz immunglobin tedavisi en sık uygulanan tedavi yöntemleriydi. Takip süreci içinde 5 hastada (%23.8) ölüm gözlendi.
Sonuç: PNS nadir görülen, tanısı zor olan sendromlar olup, sıklıkla hastaya yanlış tanı konulur yada tanı atlanabilir. Hastalarda semptom ve bulgularının erken tanınması ve uygun tanı ve tedavi planının zamanında belirlenmesi için farklı merkezden PNS ilişkili verilere ihtiyaç vardır.
References
- 1. Devine MF, Kothapalli N, Elkhooly M, Dubey D. Paraneoplastic neurological syndromes: clinical presentations and management. Ther Adv Neuro Disord. 2021; 14:1756286420985323.
- 2. Honnorat J, Antoine JC. Paraneoplastic neurological syndromes. Orphanet J Rare Dis. 2007; 2:22.
- 3. Li L, Guo Y, Wang J. Detection of paraneoplastic antibodies and their significance in paraneoplastic neurologic syndromes: a narrative review. Ann Transl Med. 2023; 11(7):283.
- 4. Graber JJ. Paraneoplastic Neurologic Syndromes. Continuum (Minneap Minn). 2023;29(6):1779-1808
- 5. Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology. 1985, 35(4):538-43.
- 6. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, et al. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004; 75(8):1135-40.
- 7. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 2000; 123 (Pt 7):1481-94.
- 8. Graus F, Vogrig A, Muniz-Castrillo S, Antoine JCG, Desestret V, Dubey D, et al. Updated diagnostic criteria for paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflamm. 2021; 8(4): e1014.
- 9. Höftberger R, Rosenfeld MR, Dalmau J. Update on neurological paraneoplastic syndromes. Curr Opin Oncol. 2015; 27(6):489-95.
- 10. Binks S, Uy C, Honnorat J, Irani SR. Paraneoplastic neurological syndromes: a practical approach to diagnosis and management. Pract Neurol. 2022; 22(1):19-31.
- 11. Giometto B, Grisold W, Vitaliani R, Graus F, Honnorat J, Bertolini G. Paraneoplastic neurologic syndrome in the PNS Euronetwork database: a European study from 20 centers. Arch Neurol. 2010; 67(3):330-5.
- 12. Şen S, Terzi M. Paraneoplastic neurologic disorders. J Exp Clin Med. 2013; 30(3):209-13.
- 13. Oliveira V, Videira G, Samões R, Carneiro P, Neves E, Santos E. Paraneoplastic neurological syndromes with onconeural antibodies: a single center retrospective study. J Neurol Sci. 2020; 418:117103.
- 14. Boyko M, Au KLK, Casault C, de Robles P, Pfeffer G. Systematic review of the clinical spectrum of CASPR2 antibody syndrome. J Neurol. 2020; 267(4):1137-46.
- 15. Tüzün E, Bebek N, Sema İ, Durmuş H, Kürtüncü M, Gürses C, et al. Amphiphysin autoimmunity: associated neurological syndromes and tumors in the Turkish population. J Neurol Sci [Turk]. 2010;27(2):121- 6
- 16. Tüzün E, Dalmau J. Limbic encephalitis and variants: classification, diagnosis and treatment. Neurologist. 2007; 13(5):261-71.
- 17. Özözen Ayas Z, Kotan D, Oguz Akarsu E, Demiryürek BE. Analysis of the patients with autoimmune neurological syndromes in a single center in Turkey. Osmangazi Journal of Med. 2021; 43(1):62-9.
- 18. Erkoyun HU, Gündoğan S, Seçil Y, Beckmann Y, İncesu TK, Türe HS, et al. Paraneoplastic neurologic syndromes: rare but more common than expected nine cases with a literature review. Turk J Neurol. 2018; 24(1):63-9.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Neurology and Neuromuscular Diseases |
| Journal Section | Original Research |
| Authors | |
| Publication Date | June 15, 2025 |
| Submission Date | July 24, 2024 |
| Acceptance Date | April 2, 2025 |
| Published in Issue | Year 2025 Volume: 15 Issue: 2 |
