Cervical dystonia: ways to achieve long-term treatment eff ects and improve patients’ quality of life

The main treatment for cervical dystonia (CD) is botulinum toxin type A (BTA) injections, but several long-term studies have found that between 19-46% of patients discontinue treatment. Anxiety and depression play a signi fi cant role in reducing the quality of life in patients with CD, according to previous surveys.

Aim: to assess the dynamics of CD symptom severity, emotional disturbance, and quality of life in patients under different treatment methods.

Material and methods. 61 patients with CD, 16 (26%) men and 45 (74%) women, age 50 [40; 59] years, duration of illness 4 [2; 7] years, age at onset 44 [34; 54] years, were studied. Changes in motor and aff ective disturbances, quality of life in patients with CD were assessed after 2 and 4 months in the context of diff erent treatment methods — BTA monotherapy, antidepressant (AD), combined therapy (AD + AD).

Results. Combination therapy (BT + AD) was shown to be superior to BTA monotherapy in long-term follow-up of patients in terms of correction of depression, anxiety, integrative assessment of quality of life and severity of dystonia. After 4 months of treatment, the (BT + AD) subgroup maintained the positive trend achieved in dystonia severity (p < 0.001). At the end of the follow-up period in the BT group, the positive eff ect of therapy had regressed to baseline levels of dystonia severity.

Conclusion. To achieve a sustained therapeutic response in patients with CD, diagnosis and appropriate correction of emotional disturbances is necessary. The potential effi cacy of antidepressants in the treatment of motor and sensory symptoms of CD requires further investigation.

1. Dauer W.T., Burke R.E., Greene P., Fahn S. Current concepts on the clinical features, aetiology and management of idiopathic cervical dystonia. Brain. 1998;121(Pt 4):547–560. https://doi:10.1093/brain/121.4.547

2. Epidemiological Study of Dystonia in Europe (ESDE) Collaborative Group. A prevalence study of primary dystonia in eight European countries. Journal of neurology. 2000;247(10):787–92. https://doi: 10.1007/s004150070094

3. Орлова О.Р. Фокальные дистонии: современные подходы к диагностике и возможности ботулинотерапии. Атмосфера. Нервные болезни. 2016;4:3–12. [Orlova O.R. Focal Dystonia:current diagnostic approach and use of botulinum toxin treatment. Atmosphere. Nervous diseases. 2016;4:3–12. (In Russ.)]. https://cyberleninka.ru/article/n/fokalnye-distonii-sovremennyepodhody-k-diagnostike-i-vozmozhnosti-botulinoterapii).

4. Орлова О.Р., Яхно Н.Н., Коренко Л.А., Скоромец А.А. Диспорт (токсин ботулизма типа А) в лечении цервикальной дистонии (спастической кривошеи). Атмосфера. Нервные болезни. 2006;2:30–34. [Orlova O.R., Yakhno N.N., Korenko L.A., Skoromets A.A. Dysport (botulinum toxin type A) in the treatment of cervical dystonia (spastic torticollis). Atmosphere. Nervous diseases. 2006;2:30–34. (In Russ.)]. https://cyberleninka.ru/article/n/disport-toksin-botulizma-tipa-a-v-lechenii-tservikalnoy-distonii-spasticheskoy-krivoshei 5. Коваленко А.П., Залялова З.А., Иволгин А.Ф. Новые подходы к лечению цервикальной дистонии. Концепция двойного навигационного контроля. Неврология, нейропсихиатрия, психосоматика. 2021;13(6):124–131. [Kovalenko A.P., Zalya lova Z.A., Ivolgin A.F. Novel approaches to the treatment of cervical dystonia. The concept of dual navigation control. Neurology, Neuropsychiatry, Psychosomatics. 2021;13(6):124–131. (In Russ.)]. https://doi.org/10.14412/2074-2711-2021-6-124-131

5. Hallett M., Albanese A., Dressler D., Segal K.R., Simpson D.M., Truong D., Jankovic J. Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disorders. Toxicon: offi cial journal of the International Society on Toxinology, 2013;67:94–114. https://doi.org/10.1016/j.toxicon.2012.12.004

6. Jankovic J. Botulinum toxin: State of the art. Movement disorders: offi cial journal of the Movement Disorder Society. 2017;32(8):1131–1138. https:// doi:10.1002/mds.27072

7. Simpson D.M., Hallett M., Ashman E.J., Comella C.L., Green M.W., Gronseth G.S., Armstrong M.J., Gloss D., Potrebic S., Jankovic J., Karp B.P., Naumann M., So Y.T., Yablon S.A. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;86(19):1818–1826. https://doi.org/10.1212/WNL.0000000000002560

8. Truong D., Brodsky M., Lew M., Brashear A., Jankovic J., Molho E. et al. Global Dysport Cervical Dystonia Study Group. Long-term effi cacy and safety of botulinum toxin type A (Dysport) in cervical dystonia. Parkinsonism & related disorders. 2010;16(5):316–323. https://doi.org/10.1016/j.parkreldis.2010.03.002

9. Charles D., Brashear A., Hauser R.A., Li H.I., Boo L.M., Brin M.F., CD 140 Study Group. Effi cacy, tolerability, and immunogenicity of onabotulinumtoxina in a randomized, doubleblind, placebo-controlled trial for cervical dystonia. Clinical neuropharmacology. 2012;35(5):208–214. https://doi.org/10.1097/WNF.0b013e31826538c7

10. Evidente V.G., Fernandez H.H., LeDoux M.S., Brashear A., Grafe S., Hanschmann A., Comella C.L. A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin(®)) in cervical dystonia. Journal of neural transmission (Vienna). 2013;120(12):1699–1707. https://doi:10.1007/s00702-013-1048-3

11. Jinnah H.A., Comella C.L., Perlmutter J., Lungu C., Hallett M., Dystonia Coalition Investigators. Longitudinal studies of botulinum toxin in cervical dystonia: Why do patients discontinue therapy? Toxicon: offi cial journal of the International Society on Toxinology. 2018;147:89–95. https://doi.org/10.1016/j.toxicon.2017.09.004

12. Sethi K.D., Rodriguez R., Olayinka B. Satisfaction with botulinum toxin treatment: a cross-sectional survey of patients with cervical dystonia. Journal of medical economics. 2012;15(3):419–423. https://doi:10.3111/13696998.2011.653726

13. Jankovic J., Adler C.H., Charles D., Comella C., Stacy M., Schwartz M. et al. Primary results from the cervical dystonia patient registry for observation of onabotulinumtoxina effi cacy (CD PROBE). Journal of the neurological sciences. 2015;349(1–2):84–93. https://doi.org/10.1016/j.jns.2014.12.030

14. Skogseid I.M., Kerty E. The course of cervical dystonia and patient satisfaction with long-term botulinum toxin A treatment. European journal of neurology. 2005;12(3):163–170. https://doi:10.1111/j.1468-1331.2004.01053.x

15. Trosch R.M., Espay A.J., Truong D., Gil R., Singer C., LeWitt P.A. et al. Multicenter observational study of abobotulinumtoxin A neurotoxin in cervical dystonia: The ANCHOR-CD registry. Journal of the neurological sciences. 2017;376:84–90. https://doi.org/10.1016/j.jns.2017.02.042

16. Misra V.P., Ehler E., Zakine B., Maisonobe P., SimonettaMoreau M; INTEREST IN CD group. Factors infl uencing response to Botulinum toxin type A in patients with idiopathic cervical dystonia: results from an international observational study. BMJ open. 2012;2(3):e000881. https://doi.org/10.1136/bmjopen-2012-000881

17. Салоухина Н.И., Нодель М.Р., Толмачева В.А. Недвигательные нарушения у пациентов с мышечной дистонией . Журнал неврологии и психиатрии имени С.С. Корсакова. 2018;118(9):98–105. [Salouchina N.I., Nodel’ M.R., Tolmacheva V.A. Non-motor disorders in patients with muscular dystonia. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2018;118(9):98–105. (In Russ.)]. https://doi:10.17116/jnevro201811809198

18. Нодель М.Р., Салоухина Н.И., Толмачева В.А. Влияние недвигательных расстройств на качество жизни пациентов с цервикальной мышечной дистонией .Неврология,нейропсихиатрия, психосоматика. 2022;14(3):19–25. [Nodel M.R., Salouhina N.I., Tolmacheva V.A. The impact of non-motor disorders on the quality of life of patients with cervical muscular dystonia. Neurology, Neuropsychiatry, Psychosomatics. 2022;14(3):19–25. (In Russ.)]. https://doi: 10.14412/2074-2711-2022-3-19-25

19. Толмачева В.А., Юзбашян П.Г., Петелин Д.С., Волель Б.А., Салоухина Н.И., Нодель М.Р., Романов Д.В. Расстройства тревожно-депрессивного спектра при цервикальной дистонии. Неврология, нейропсихиатрия, психосоматика. 2022;14(4):38–43. [Tolmacheva V.A., Yuzbashyan P.G., Petelin D.S., Volel B.A., Salouhina N.I., Nodel M.R., Romanov D.V. Anxiety-depressive spectrum disorders in cervical dystonia. Neurology, Neuropsychiatry, Psychosomatics. 2022;14(4):38–43. (In Russ.)]. https://doi: 10.14412/2074-2711-2022-4-38-43

20. Consky E.S., Basinki A., Belle L., Ranawaya R., Lang A.E. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS): assessment of validity and inter-rater reliability. Neurology. 1990;40(suppl 1):445.

21. Müller J., Wissel J., Kemmler G., Voller B., Bodner T., Schneider A. et al. Craniocervical dystonia questionnaire (CDQ-24): development and validation of a disease-specifi c quality of life instrument. Journal of neurology, neurosurgery, and psychiatry. 2004;75(5):749–753. https://doi.org/10.1136/jnnp.2003.013441

22. Beck A.T., Steer R.A., Ball R., Ranieri W. Comparison of Beck Depression Inventories-IA and -II in psychiatric outpatients. J Pers Assess. 1996;67(3):588–597. https://doi:10.1207/s15327752jpa6703_13

23. Ханин Ю.Л. Краткое руководство к применению шкалы реактивной, личностной тревожности Ч.Д. Спилбергера. Ленинград: ЛНИИФК, 1976:40 с. [Khanin Yu.L. A Brief Guide to applying the scale of Reactive Personal Anxiety by Ch.D. Spielberger. Leningrad, RF: LNIIFK; 1976:40 р. (In Russ.)].

24. Zetterberg L., Aquilonius S.M., Lindmark B. Impact of dystonia on quality of life and health in a Swedish population. Acta neurologica Scandinavica. 2009;119(6):376–382. https://doi:10.1111/j.1600-0404.2008.01111.x

25. Torres J.A.K.L., Rosales R.L. Nonmotor Symptoms in Dystonia. International review of neurobiology. 2017;134:1335–1371. https://doi:10.1016/bs.irn.2017.05.003

26. Novaretti N., Cunha A.L.N., Bezerra T.C., Pena Pereira M.A., de Oliveira D.S., Macruz Brito M.M.C. et al. The Prevalence and Correlation of Non-motor Symptoms in Adult Patients with Idiopathic Focal or Segmental Dystonia. Tremor and other hyperkinetic movements (New York, N.Y.). 2019;9:596. https://doi.org/10.7916/fhnv-v355

27. Иванникова Е.И., Крыжановский С.М., Самушия М.А., Ковешникова О.А., Иволгин А.Ф., Авсей цева Т.Ю. Психическая патология при цервикальной дистонии. Кремлевская медицина. Клинический вестник. 2021;3:34–41. [Ivannikova E.I., Kryzhanovsky S.M., Samushiya M.A., Koveshnikova O.A., Ivolgin A.F., Avseitseva T.Yu. Psychiatric disorders in cervical dystonia. Kremlin Medicine. Clinical Bulletin. 2021;3:34–41. (In Russ.)]. https://doi:10.26269/zgzy-1a79

28. Хаятова З.Г., Залялова З.А. Клинические варианты аффективных, диссомнических и двигательных проявлений краниоцервикальной дистонии (обзор литературы). Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева. 2020;(2):47–56. [Khaiatova Z.G., Zalyalova Z.A. Clinical variety of aff ective, sleep and motor manifestations in craniocervical dystonia (a literature review). V.M. Bekhterev review of psychiatry and medical psychology. 2020;(2):47–56. (In Russ.)]. https://doi.org/10.31363/2313-7053-2020-2-47-56

29. Berardelli I., Ferrazzano G., Pasquini M., Biondi M., Berardelli A., Fabbrini G. Clinical course of psychiatric disorders in patients with cervical dystonia. Psychiatry research. 2015;229(1–2):583–585. https://doi:10.1016/j.psychres.2015.07.076

30. Zoons E., Booij J., Delnooz C.C.S., Dijk J.M., Dreissen Y.E.M., Koelman J.H.T.M. et al. Randomised controlled trial of escitalopram for cervical dystonia with dystonic jerks/tremor. Journal of neurology, neurosurgery, and psychiatry. 2018;89(6):579–585. https://doi.org/10.1136/jnnp-2017-317352

31. Zoons E., Booij J., Speelman J. D., Dreissen Y.E.M., Smit M., Tijssen M.A.J. Lower serotonin transporter binding in patients with cervical dystonia is associated with psychiatric symptoms. EJNMMI research. 2017;7(1):87. https://doi.org/10.1186/s13550-017-0338-4

32. Smit M., Vállez García D., de Jong B.M., Zoons E., Booij J., Dierckx R.A. et al. Relationships between Serotonin Transporter Binding in the Raphe Nuclei, Basal Ganglia, and Hippocampus with Clinical Symptoms in Cervical Dystonia: A [11C]DASB Positron Emission Tomography Study. Frontiers in neurology. 2018;9:88. https://doi.org/10.3389/fneur.2018.00088

33. Zoons E., Tijssen M.A.J., Dreissen Y.E.M., Smit M., Booij J. The Eff ect of Escitalopram on Central Serotonergic and Dopaminergic Systems in Patients with Cervical Dystonia, and Its Relationship with Clinical Treatment Eff ects: A Double-Blind Placebo-Controlled Trial. Biomolecules. 2020;10(6):880. https://doi:10.3390/biom10060880