Pain relief in cervical dystonia following regular long-term botulinum therapy

Close metadata

INTRODUCTION

Cervical dystonia (CD) is characterized by pain, which is often the main reason for visiting a doctor. Analgesics are often used to control pain, but regular administration of botulinum toxin type A (BTA) may be more effective. The effectiveness of regular long-term use of BTA in CD in relation to pain has been little studied, which served as the basis for this study.

MATERIAL AND METHODS

For 3 years, 65 patients (44 men, 21 women, average age 53±15 years) with CD who regularly received BTA therapy were observed. The severity of CD was assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), pain — using TWSTRS and a Numeric Rating Scale (NRS) at baseline, one month after BTA therapy and 3 years later during the period of maximum severity of symptoms (before the next BTA injection).

RESULTS

A decrease in pain according to NRS and TWSTRS was shown not only after 1 month, but also after 3 years (p<0.0001). The reduction in pain was significant for initially moderate and severe pain according to the NRS of pain (p<0.0001). In patients with mild pain intensity, no significant changes were noted (F=1.5, p=0.23). An inverse correlation was noted between the sensory trick and the duration of the disease.

CONCLUSION

The use of BTA for CD reduces pain not only after a month, but also after 3 years of regular therapy during the period of maximum severity of symptoms.

Keywords:

cervical dystonia

pain

TWSTRS

botulinum therapy

Authors:

Tolmacheva V.A.

Sechenov First Moscow State Medical University (Sechenov University)

ORCID: 0000-0002-8115-2668

Spektor E.D.

Sechenov First Moscow State Medical University (Sechenov University)

ORCID: 0000-0003-0714-9476

Romanov D.V.

Sechenov First Moscow State Medical University (Sechenov University);
Scientific Center of Mental Health

ORCID: 0000-0002-1822-8973

Parfenov V.A.

Sechenov First Moscow State Medical University

SPIN RSCI: 3322-5559
Scopus AuthorID: 57216913889
ResearcherID: AAG-7021-2019
ORCID: 0000-0002-1992-7960

Received:

17.11.2023

Accepted:

12.01.2024

List of references:

Castagna A, Albanese A. Management of cervical dystonia with botulinum neurotoxins and EMG/ultrasound guidance. Neurol Clin Pract. 2019;9(1):64-73. https://doi.org/10.1212/CPJ.0000000000000568
Defazio G, Esposito M, Abbruzzese G, Scaglione CL, Fabbrini G, Ferrazzano G, Peluso S, Pellicciari R, Gigante AF, Cossu G, Arca R, Avanzino L, Bono F, Mazza MR, Bertolasi L, Bacchin R, Eleopra R, Lettieri C, Morgante F, Altavista MC, Polidori L, Liguori R, Misceo S, Squintani G, Tinazzi M, Ceravolo R, Unti E, Magistrelli L, Coletti Moja M, Modugno N, Petracca M, Tambasco N, Cotelli MS, Aguggia M, Pisani A, Romano M, Zibetti M, Bentivoglio AR, Albanese A, Girlanda P, Berardelli A. The Italian Dystonia Registry: rationale, design and preliminary findings. Neurol Sci. 2017;38(5):819-825. Epub 2017 Feb 18. Erratum in: Neurol Sci. 2018; PMID: 28215037. https://doi.org/10.1007/s10072-017-2839-3
Di Biasio F, Marchese R, Abbruzzese G, Baldi O, Esposito M, Silvestre F, Tescione G, Berardelli A, Fabbrini G, Ferrazzano G, Pellicciari R, Eleopra R, Devigili G, Bono F, Santangelo D, Bertolasi L, Altavista MC, Moschella V, Barone P, Erro R, Albanese A, Scaglione C, Liguori R, Cotelli MS, Cossu G, Ceravolo R, Coletti Moja M, Zibetti M, Pisani A, Petracca M, Tinazzi M, Maderna L, Girlanda P, Magistrelli L, Misceo S, Romano M, Minafra B, Modugno N, Aguggia M, Cassano D, Defazio G, Avanzino L. Motor and Sensory Features of Cervical Dystonia Subtypes: Data From the Italian Dystonia Registry. Front Neurol. 2020;11:906. https://doi.org/10.3389/fneur.2020.00906
Tinazzi M, Erro R, Mascia MM, Esposito M, Ercoli T, Ferrazzano G, Di Biasio F, Pellicciari R, Eleopra R, Bono F, Bertolasi L, Barone P, Scaglione CLM, Pisani A, Altavista MC, Cotelli MS, Ceravolo R, Cossu G, Zibetti M, Moja MC, Girlanda P, Maderna L, Albanese A, Petracca M, Magistrelli L, Misceo S, Minafra B, Romano M, Squintani GM, Modugno N, Aguggia M, Cassano D, Castagna A, Morgante F, Berardelli A, Defazio G. Demographic and clinical determinants of neck pain in idiopathic cervical dystonia. J Neural Transm (Vienna). 2020;127(10):1435-1439. Epub 2020 Aug 26. Erratum in: J Neural Transm (Vienna). 2020 Oct 20; PMID: 32851476. https://doi.org/10.1007/s00702-020-02245-4
Ramos VF, Karp BI, Hallett M. Tricks in dystonia: ordering the complexity. J Neurol Neurosurg Psychiatry. 2014;85(9):987-993. https://doi.org/10.1136/jnnp-2013-306971
Berman BD, Groth CL, Sillau SH, Pirio Richardson S, Norris SA, Junker J, Brüggemann N, Agarwal P, Barbano RL, Espay AJ, Vizcarra JA, Klein C, Bäumer T, Loens S, Reich SG, Vidailhet M, Bonnet C, Roze E, Jinnah HA, Perlmutter JS. Risk of spread in adult-onset isolated focal dystonia: a prospective international cohort study. J Neurol Neurosurg Psychiatry. 2020;91(3):314-320. https://doi.org/10.1136/jnnp-2019-321794
Abbruzzese G, Berardelli A, Girlanda P, Marchese R, Martino D, Morgante F, Avanzino L, Colosimo C, Defazio G. Long-term assessment of the risk of spread in primary late-onset focal dystonia. J Neurol Neurosurg Psychiatry. 2008;79(4):392-396. https://doi.org/10.1136/jnnp.2007.124594
Ercoli T, Erro R, Fabbrini G, Pellicciari R, Girlanda P, Terranova C, Avanzino L, Di Biasio F, Barone P, Esposito M, De Joanna G, Eleopra R, Bono F, Manzo L, Bentivoglio AR, Petracca M, Mascia MM, Albanese A, Castagna A, Ceravolo R, Altavista MC, Scaglione C, Magistrelli L, Zibetti M, Bertolasi L, Coletti Moja M, Cotelli MS, Cossu G, Minafra B, Pisani A, Misceo S, Modugno N, Romano M, Cassano D, Berardelli A, Defazio G; Italian Dystonia Registry Participants. Spread of segmental/multifocal idiopathic adult-onset dystonia to a third body site. Parkinsonism Relat Disord. 2021;87:70-74. https://doi.org/10.1016/j.parkreldis.2021.04.022
Defazio G, Ercoli T, Erro R, Pellicciari R, Mascia MM, Fabbrini G, Albanese A, Lalli S, Eleopra R, Barone P, Marchese R, Ceravolo R, Scaglione C, Liguori R, Esposito M, Bentivoglio AR, Bertolasi L, Altavista MC, Bono F, Pisani A, Girlanda P, Berardelli A; Italian Dystonia Registry Participants. Idiopathic Non-task-Specific Upper Limb Dystonia, a Neglected Form of Dystonia. Mov Disord. 2020;35(11):2038-2045. https://doi.org/10.1002/mds.28199
Chan J, Brin MF, Fahn S. Idiopathic cervical dystonia: clinical characteristics. Mov Disord. 1991;6(2):119-126. PMID: 2057004. https://doi.org/10.1002/mds.870060206
Jankovic J, Leder S, Warner D, Schwartz K. Cervical dystonia: clinical findings and associated movement disorders. Neurology. 1991;41(7):1088-1091. https://doi.org/10.1212/wnl.41.7.1088
Avenali M, De Icco R, Tinazzi M, Defazio G, Tronconi L, Sandrini G, Tassorelli C. Pain in focal dystonias — A focused review to address an important component of the disease. Parkinsonism Relat Disord. 2018;54:17-24. https://doi.org/10.1016/j.parkreldis.2018.04.030
Charles PD, Adler CH, Stacy M, Comella C, Jankovic J, Manack Adams A, Schwartz M, Brin MF. Cervical dystonia and pain: characteristics and treatment patterns from CD PROBE (Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy). J Neurol. 2014;261(7):1309-1319. https://doi.org/10.1007/s00415-014-7343-6
Novak I, Campbell L, Boyce M, Fung VS; Cerebral Palsy Institute. Botulinum toxin assessment, intervention and aftercare for cervical dystonia and other causes of hypertonia of the neck: international consensus statement. Eur J Neurol. 2010;17(suppl 2):94-108. https://doi.org/10.1111/j.1468-1331.2010.03130.x
Blackie JD, Lees AJ. Botulinum toxin treatment in spasmodic torticollis. J Neurol Neurosurg Psychiatry. 1990;53(8):640-643. https://doi.org/10.1136/jnnp.53.8.640
Kutvonen O, Dastidar P, Nurmikko T. Pain in spasmodic torticollis. Pain. 1997;69(3):279-286. https://doi.org/10.1016/S0304-3959(96)03296-4
Kulisevsky J, Lleó A, Gironell A, Molet J, Pascual-Sedano B, Parés P. Bilateral pallidal stimulation for cervical dystonia: dissociated pain and motor improvement. Neurology. 2000;55(11):1754-1755. https://doi.org/10.1212/wnl.55.11.1754
Tinazzi M, Squintani GM, Bhatia KP, Segatti A, Donato F, Valeriani M, Erro R. Pain in cervical dystonia: Evidence of abnormal inhibitory control. Parkinsonism Relat Disord. 2019;65:252-255. https://doi.org/10.1016/j.parkreldis.2019.06.009
Kuyper DJ, Parra V, Aerts S, Okun MS, Kluger BM. Nonmotor manifestations of dystonia: A systematic review. Mov Disord. 2011;26(7):1206-1217. https://doi.org/10.1002/mds.23709
Chudler EH, Dong WK. The role of the basal ganglia in nociception and pain. Pain. 1995;60(1):3-38. https://doi.org/10.1016/0304-3959(94)00172-B
Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013;28(7):863-873. https://doi.org/10.1002/mds.25475
Defazio G, Jankovic J, Giel JL, Papapetropoulos S. Descriptive epidemiology of cervical dystonia. Tremor Other Hyperkinet Mov (N Y). 2013;3:tre-03-193-4374-2. https://doi.org/10.7916/D80C4TGJ
Brugger F, Peters A, Georgiev D, Kägi G, Balint B, Bhatia KP, Day BL. Sensory trick efficacy in cervical dystonia is linked to processing of neck proprioception. Parkinsonism Relat Disord. 2019;61:50-56. https://doi.org/10.1016/j.parkreldis.2018.11.029
Coombes SA, Misra G. Pain and motor processing in the human cerebellum. Pain. 2016;157(1):117-127. https://doi.org/10.1097/j.pain.0000000000000337
Baarbé JK, Yielder P, Haavik H, Holmes MWR, Murphy BA. Subclinical recurrent neck pain and its treatment impacts motor training-induced plasticity of the cerebellum and motor cortex. PLoS One. 2018;13(2):e0193413. https://doi.org/10.1371/journal.pone.0193413
Naumann M, Magyar-Lehmann S, Reiners K, Erbguth F, Leenders KL. Sensory tricks in cervical dystonia: perceptual dysbalance of parietal cortex modulates frontal motor programming. Ann Neurol. 2000;47(3):322-328.
Tinazzi M, Erro R, Mascia MM, Esposito M, Ercoli T, Ferrazzano G, Di Biasio F, Pellicciari R, Eleopra R, Bono F, Bertolasi L, Barone P, Scaglione CLM, Pisani A, Altavista MC, Cotelli MS, Ceravolo R, Cossu G, Zibetti M, Moja MC, Girlanda P, Maderna L, Albanese A, Petracca M, Magistrelli L, Misceo S, Minafra B, Romano M, Squintani GM, Modugno N, Aguggia M, Cassano D, Castagna A, Morgante F, Berardelli A, Defazio G. Demographic and clinical determinants of neck pain in idiopathiccervicaldystonia. J Neural Transm (Vienna). 2020;127(10):1435-1439. https://doi.org/10.1007/s00702-020-02245-4
Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9(2):105-21. https://doi.org/10.1016/j.jpain.2007.09.005
Charles PD, Manack Adams A, Davis T, Bradley K, Schwartz M, Brin MF, Patel AT. Neck Pain and Cervical Dystonia: Treatment Outcomes from CD PROBE (Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy). PainPract. 2016;16(8):1073-1082. https://doi.org/10.1111/papr.12408
Colhado OC, Boeing M, Ortega LB. Botulinum toxin in pain treatment. Rev Bras Anestesiol. 2009;59(3):366-381. (In English, Portuguese). https://doi.org/10.1590/s0034-70942009000300013
Aoki KR, Francis J. Updates on the antinociceptive mechanism hypothesis of botulinum toxin A. Parkinsonism Relat Disord. 2011;17(suppl 1):S28-S33. https://doi.org/10.1016/j.parkreldis.2011.06.013
Da Silva LB, Kulas D, Karshenas A, Cairns BE, Bach FW, Arendt-Nielsen L, Gazerani P. Time course analysis of the effects of botulinum neurotoxin type A on pain and vasomotor responses evoked by glutamate injection into human temporalis muscles. Toxins (Basel). 2014;6(2):592-607. https://doi.org/10.3390/toxins6020592
Pavone F, Luvisetto S. Botulinum neurotoxin for pain management: insights from animal models. Toxins (Basel). 2010;2(12):2890-2913. https://doi.org/10.3390/toxins2122890
Burstein R, Zhang X, Levy D, Aoki KR, Brin MF. Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications for migraine and other pains. Cephalalgia. 2014;34(11):853-869. https://doi.org/10.1177/0333102414527648
Relja M, Telarovic S. Botulinum toxin type-A and pain responsiveness in cervical dystonia: A dose response study. Mov Disord. 2005;20:S23.
Wissel J, Ganapathy V, Ward AB, Borg J, Ertzgaard P, Herrmann C, Haggstrom A, Sakel M, Ma J, Dimitrova R, Fulford-Smith A, Gillard P. OnabotulinumtoxinA Improves Pain in Patients With Post-Stroke Spasticity: Findings From a Randomized, Double-Blind, Placebo-Controlled Trial. J Pain Symptom Manage. 2016;52(1):17-26. https://doi.org/10.1016/j.jpainsymman.2016.01.007
Colosimo C, Charles D, Misra VP, Maisonobe P, Om S; INTEREST IN CD2 study group. Cumulative effects of long-term treatment with abobotulinumtoxinA in cervical dystonia: Findings from a prospective, observational study. J Neurol Sci. 2020;416:117015. https://doi.org/10.1016/j.jns.2020.117015
Comella C, Hauser RA, Isaacson SH, Truong D, Oguh O, Hui J, Molho ES, Brodsky M, Furr-Stimming E, Comes G, Hast MA, Charles D. Efficacy and safety of two incobotulinumtoxinA injection intervals in cervical dystonia patients with inadequate benefit from standard injection intervals of botulinum toxin: Phase 4, open-label, randomized, noninferiority study. Clin Park Relat Disord. 2022;6:100142. https://doi.org/10.1016/j.prdoa.2022.100142
Dressler D, Paus S, Seitzinger A, Gebhardt B, Kupsch A. Long-term efficacy and safety of incobotulinumtoxinA injections in patients with cervical dystonia. J Neurol Neurosurg Psychiatry. 2013;84(9):1014-9. https://doi.org/10.1136/jnnp-2012-303608
Salnikova VA, Antipenko EA, Erokhina MN. Pain in muscular dystonia, the possibility of botulinum therapy. Russian Journal of Pain. 2019;17(1):17-21. (In Russ.). https://doi.org/10.25731/rasp.2019.01.03
Jost WH, Hefter H, Stenner A, Reichel G. Rating scales for cervical dystonia: a critical evaluation of tools for outcome assessment of botulinum toxin therapy. J Neural Transm (Vienna). 2013;120(3):487-496. Epub 2012 Aug 17. https://doi.org/10.1007/s00702-012-0887-7
Benecke R, Jost WH, Kanovsky P, Ruzicka E, Comes G, Grafe S. A newbotulinum toxin type A free of complexing proteins for treatment of cervical dystonia. Neurology. 2005;64(11):1949-51. https://doi.org/10.1212/01.WNL.0000163767.99354.C3
Comella CL, Jankovic J, Truong DD, Hanschmann A, Grafe S; U.S. XEOMIN Cervical Dystonia Study Group. Efficacy and safety of incobotulinumtoxinA (NT 201, XEOMIN®, botulinum neurotoxin type A, without accessory proteins) in patients with cervical dystonia. J Neurol Sci. 2011; 308(1-2):103-109. https://doi.org/10.1016/j.jns.2011.05.041
Evidente VG, Fernandez HH, LeDoux MS, Brashear A, Grafe S, Hanschmann A, Comella CL. A randomized, double-blind study of repeated incobotulinumtoxinA (Xeomin) in cervical dystonia. J Neural Transm (Vienna). 2013;120(12):1699-707. https://doi.org/10.1007/s00702-013-1048-3
Tolmacheva VA, Petelin DS, Volel BA. Comprehensive diagnosis of cervical dystonia and the efficacy of long-term (three-year) botulinum therapy. Neurology, Neuropsychiatry, Psychosomatics. 2023;15(5):35-38. (In Russ.). https://doi.org/10.14412/2074-27112023-5-35-38
Klingelhoefer L, Kaiser M, Sauerbier A, Untucht R, Wienecke M, Mammadova K, Falkenburger B, Gregor O, Chaudhuri KR, Reichmann H. Emotionalwell-being and pain could be a greater determinant of quality of life compared to motor severity in cervical dystonia. J Neural Transm (Vienna). 2021;128(3):305-314. https://doi.org/10.1007/s00702-020-02274-z
Tolmacheva VA, Yuzbashyan PG, Petelin DS, Volel BA, Saloukhina NI, Nodel MR, Romanov DV. Anxiety-depressive spectrum disorders in cervical dystonia. Neurology, Neuropsychiatry, Psychosomatics. 2022;14(4):38-43. (In Russ.). https://doi.org/10.14412/2074-2711-2022-4-38-43
Camargo CH, Cattai L, Teive HA. Pain Relief in Cervical Dystonia with Botulinum Toxin Treatment. Toxins (Basel). 2015;7(6):2321-2335. https://doi.org/10.3390/toxins7062321
Comella CL, Jankovic J, Shannon KM, Tsui J, Swenson M, Leurgans S, Fan W; Dystonia Study Group. Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia. Neurology. 2005;65(9):1423-1429. https://doi.org/10.1212/01.wnl.0000183055.81056.5c
Quagliato EM, Carelli EF, Viana MA. A prospective, randomized, double-blind study comparing the efficacy and safety of type a botulinum toxins botox and prosigne in the treatment of cervical dystonia. Clin Neuropharmacol. 2010;33(1):22-26. https://doi.org/10.1097/WNF.0b013e3181c46f48
Pappert EJ, Germanson T; Myobloc/Neurobloc European Cervical Dystonia Study Group. Botulinum toxin type B vs. type A in toxin-naïve patients with cervical dystonia: Randomized, double-blind, noninferiority trial. Mov Disord. 2008;23(4):510-517. https://doi.org/10.1002/mds.21724

Close metadata