Salivary gland immunohistochemistry vs substantia nigra sonography: comparative analysis of diagnostic significance

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Abstract

Introduction. Parkinson's disease (PD) urges for new instrumental methods of diagnosis. Transcranial sonography of the substantia nigra (SN TCS) is an established method for early PD diagnosis but its application is limited. Recently, biopsies (primarily that of salivary gland) and test for abnormal α-synuclein are suggested to verify PD.

Materials and methods. We assessed 12 individuals with PD, Hoehn–Yahr 2.3 ± 0.4. The assessments included: UPDRS, NMSQ, NMSS, RBDSQ, PDQ-8, MoCA, and HADS scoring; SN TCS; and sublingual gland immunohistochemistry for phosphorylated α-synuclein (PS-129) with automated morphometric analysis.

Results. Substantia nigra hyperechogenicity was shown in 75% of patients whereas biopsy revealed PS-129 in 100% of patients. Echogenic area of the substantia nigra was 0.24 [0.21; 0.3] cm2. PS-129 inclusion area varied from 28.47 [27.55; 96.26] to 238.77 [234.13; 272.49] μm2, and PS-129 proportion varied from 13.4% to 93.4% of the nervous fiber area across the patients. We found relations between PS-129 and NMSQ (r = 0.8; p < 0.001), NMSS (r = 0.9; p < 0.001), PDQ-8 (r = 0.7; p = 0.003), UPDRS-I (r = 0.7; p = 0.009), UPDRS-II (r = 0.6; p = 0.03), and HADS (anxiety r = 0.8; p = 0.002; depression r = 0.6; p = 0.04) scores.

Conclusion. The results demonstrate a higher biopsy sensitivity as compared to SN TCS. Automated morphometric analysis has been newly applied to assess PS-129 occurrence. Immunohistochemistry results are directly related to non-motor symptom severity, which may indicate high probability of PS-129 presence and diagnosis confirmation in early disease.

About the authors

Kristina K. Khacheva

Research Center of Neurology

Author for correspondence.
Email: christina.khacheva@gmail.com
ORCID iD: 0000-0001-9441-4797

Neurologist, Research Assistant, Laboratory of Neuromorphology, Research Center of Neurology

Russian Federation, Moscow

Alexey V. Karabanov

Research Center of Neurology

Email: doctor.karabanov@mail.ru
ORCID iD: 0000-0002-2174-2412

Cand. Sci. (Med.), Neurologist, Research Center of Neurology

Russian Federation, Moscow

Rinat R. Bogdanov

M.F. Vladimirsky Moscow Regional Research and Clinical Institute

Email: moniki-nevrol@mail.ru
SPIN-code: 4439-3165

D. Sci. (Med.), Professor, Department of neurology, M.F. Vladimirsky Moscow Regional Research and Clinical Institute

Russian Federation, Moscow

Dmitry N. Voronkov

Research Center of Neurology

Email: voronkovdm@gmail.com
ORCID iD: 0000-0001-5222-5322

Cand. Sci. (Med.), Senior Researcher, Laboratory of Neuromorphology, Research Center of Neurology

Russian Federation, Moscow

Valery B. Sobolev

Research Center of Neurology

Email: sobolevalera@gmail.com
ORCID iD: 0000-0002-7704-1092

Junior Researcher, Laboratory of Neuromorphology, Research Center of Neurology

Russian Federation, Moscow

Andrey O. Chechetkin

Research Center of Neurology

Email: andreychechetkin@gmail.com
ORCID iD: 0000-0002-8726-8928

D. Sci. (Med.), Head, Laboratory of Ultrasound Studies, Research Center of Neurology

Russian Federation, Moscow

Anastasiya D. Danilova

M.F. Vladimirsky Moscow Regional Research and Clinical Institute

Email: moniki-nevrol@mail.ru
ORCID iD: 0000-0003-4217-6736

Cand. Sci. (Med.), Maxillo-Facial Surgeon, M.F. Vladimirsky Moscow Regional Research and Clinical Institute

Russian Federation, Moscow

Alexander M. Sipkin

M.F. Vladimirsky Moscow Regional Research and Clinical Institute

Email: moniki-nevrol@mail.ru
ORCID iD: 0000-0001-8287-741X

D. Sci. (Med.), Leading Researcher, Head, Maxillo-Facial Surgery Department, M.F. Vladimirsky Moscow Regional Research and Clinical Institute

Russian Federation, Moscow

Sergey N. Illarioshkin

Research Center of Neurology

Email: snillario@gmail.com
ORCID iD: 0000-0002-2704-6282

D. Sci. (Med.), Prof., RAS Full Member, Director, Brain Institute, Deputy Director for Science, Research Center of Neurology

Russian Federation, Moscow

References

  1. Иллариошкин С.Н. Современные представления об этиологии болезни Паркинсона. Неврологический журнал. 2015; 20(4): 4–13. Illarioshkin S.N. Modern view on etiology of Parkinson’s disease. Neurological Journal. 2015; 20(4): 4–13. (In Russ.)
  2. Федотова Е.Ю., Чечеткин А.О., Иллариошкин С.Н. Возможности транскраниальной сонографии в диагностике экстрапирамидных заболеваний. Анналы клинической и экспериментальной неврологии. 2010; 4(4): 43–50. Fedotova E.Y., Chechetkin A.O., Illarioshkin S.N. Possibilities of transcranial sonography in extrapyramidal disorders. Annals of Clinical and Experimental Neurology. 2010; 4(4): 43–50. (In Russ.) doi: https://doi.org/10.17816/psaic322
  3. Bjorklund G., Stejskal V., Urbina M.A. et al. Metals and Parkinson’s disease: mechanisms and biochemical processes. Curr. Med. Chem. 2018; 25(19): 2198–2214.
  4. Jeong S., Jang W., Shin D.W. Association of statin use with Parkinson’s disease: dose-response relationship. Mov. Disord. 2019; 34(7):1014–1021. doi: 10.1002/mds.27681
  5. Azizova T.V., Banikova M.V., Grigoryeva E.S. et al. Occupational exposure to chronic ionizing radiation increases risk of Parkinson’s disease incidence in Russian Mayak workers. Int. J. Epidemiol. 2020; 49(2): 435–447. doi: 10.1093/ije/dyz230
  6. Benassi B., Filomeni G., Montagna C. et al. Extremely low frequency magnetic field (ELF-MF) exposure sensitizes SH-SY5Y cells to the pro-Parkinson’s disease toxin MPP+. Mol. Neurobiol. 2016; 53(6): 4247–4260. doi: 10.1007/s12035-015-9354-4
  7. Avanipully J.N., Thekkekkara D., Sahyadri M. et al. The role of olfactory system in the etiogenesis of Parkinson’s diseases: an overview. J. Pharmacol. Pharmacother. 2022; 13(1): 31–39. doi: 10.1177/0976500X221085802
  8. Spillantini M.G., Goedert M. Synucleinopathies: past, present and future. Neuropathol. Appl. Neurobiol. 2016; 42(1): 3–5. doi: 10.1111/nan.12311
  9. Braak H., Del Tredici K., Rüb U. et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging. 2003; 24(2): 197–211. doi: 10.1016/s0197-4580(02)00065-9
  10. Jellinger K.A. Synuclein deposition and non-motor symptoms in Parkinson disease. J. Neurol. Sci. 2011; 310(1–2): 107–111. doi: 10.1016/j.jns.2011.04.012
  11. Сальков В.Н., Воронков Д.Н., Хачева К.К. и др. Клинико-морфологический анализ случая болезни Паркинсона. Архив патологии. 2020; 82(2): 52–56. Sal’kov V.N., Voronkov D.N., Khacheva K.K. et al. Clinical and morphological analysis of a caseof Parkinson’s disease. Pathology Archive. 2020; 82(2): 52–56. (In Russ.) doi: 10.17116/patol20208202152
  12. Postuma R.B., Berg D., Stern M. et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov. Disord. 2015; 30(12): 1591–1601. doi: 10.1002/mds.26424
  13. Beach T.G., Adler C.H. Importance of low diagnostic accuracy for early Parkinson’s disease. Mov. Disord. 2018; 33(10): 1551–1554. doi: 10.1002/mds.27485
  14. Кравченко М.А., Чечеткин А.О. К вопросу об изучении природы ультразвукового феномена гиперэхогенности черной субстанции. Бюллетень Национального общества по изучению болезни Паркинсона и расстройств движений. 2019; (3): 15–20. Kravchenko M.A., Chechetkin A.O. On the question of studying the nature of the ultrasonic phenomenon of hyperechogenicity of the substantia nigra. Bulletin of the National Society for the Study of Parkinson’s Disease and Movement Disorders. 2019; (3): 15–20. (In Russ.) doi: 10.24411/2226-079Х-2019-12128
  15. Mei Y.L., Yang J., Wu Z.R. et al. Transcranial sonography of the substantia nigra for the differential diagnosis of Parkinson’s disease and other movement disorders: a meta-analysis. Parkinsons Dis. 2021; 2021: 8891874. doi: 10.1155/2021/8891874
  16. Visanji N.P., Mollenhauer B., Beach T.G. et al. The systemic synuclein sampling study: toward a biomarker for Parkinson’s disease. Biomark. Med. 2017; 11(4): 359–368. doi: 10.2217/bmm-2016-0366
  17. Соболев В.Б., Худоерков Р.М Иммуногистохимическое выявление α-синуклеина в слюнной железе как биомаркер болезни Паркинсона. Бюллетень Национального общества по изучению болезни Паркинсона и расстройств движений. 2017; (2): 16–23. Sobolev V.B., Khudoyerkov R.M. Immunohistochemical detection of α-synucle-in in the salivary gland as a biomarker of Parkinson’s disease. Bulletin of the National Society for the Study of Parkinson’s Disease and Movement Disorders. 2017; (2): 16–23. (In Russ.)
  18. Pouclet H., Lebouvier T., Coron E. et al. A comparison between rectal and colonic biopsies to detect Lewy pathology in Parkinson’s disease. Neurobiol. Dis. 2012; 45(1): 305–309. doi: 10.1016/j.nbd.2011.08.014
  19. Adler C.H., Dugger B.N., Hinni M.L. et al. Submandibular gland needle biopsy for the diagnosis of Parkinson disease. Neurology. 2014; 82(10): 858–864. doi: 10.1212/WNL.0000000000000204
  20. Sobolev V.B., Voronkov D.N., Khudoerkov R.M. Treatment of histological material for the detection phosphotylated and unphosphorilated apha-synuclein. Аsymmetry. 2016; 10(4): 77–84.
  21. Гуменюк И.С., Чуприненко Л.М., Сотниченко А.С. и др. Автоматизированный морфометрический анализ как метод определения содержания компонентов внеклеточного матрикса и количественной оценки ядерных антигенов. Архив патологии. 2017; 79(5): 49–56. Gumenyuk I.S., Chuprinenko L.M., Sotnichenko A.S. et al. Automatic morphometric analysis as a method for determining the level of extracellular matrix components and for quantifying nuclear antigens. Pathology Archive. 2017; 79(5): 49–56. (In Russ.) doi: 10.17116/patol201779549-56
  22. Kalia L.V., Lang A.E., Hazrati L.N. et al. Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol. 2015; 72(1): 100–105. doi: 10.1001/jamaneurol.2014.2704
  23. Wang W., Song N., Jia F. et al. Genomic DNA levels of mutant alpha-synuclein correlate with non-motor symptoms in an A53T Parkinson’s disease mouse model. Neurochem. Int. 2018; 114: 71–79. doi: 10.1016/j.neuint.2018.01.006
  24. Jafari S., Etminan M., Aminzadeh F., Samii A. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov. Disord. 2013; 28(9): 1222–1229. doi: 10.1002/mds.25458

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Copyright (c) 2023 Khacheva K.K., Karabanov A.V., Bogdanov R.R., Voronkov D.N., Sobolev V.B., Chechetkin A.O., Danilova A.D., Sipkin A.M., Illarioshkin S.N.

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