Cerebellar ataxia, neuropathy and bilateral vestibular areflexia (CANVAS) is a rare neurodegenerative disease affecting the cerebellum, the peripheral nervous system and the vestibular system. Due to the lack of approved drugs, therapy comprises physiotherapy and speech therapy. Transcranial magnetic stimulation is a promising non-invasive therapeutic option to complement classical symptomatic therapies.
OBJECTIVE:
To test feasibility of the combination of transcranial magnetic stimulation using an accelerated protocol and standard symptomatic therapy in patients with CANVAS.
METHODS:
Eight patients with genetically confirmed CANVAS were assigned to either verum or sham cerebellar transcranial magnetic stimulation using an accelerated protocol. Treatment duration was limited to 5 days. Additionally, patients in both groups received symptomatic therapy (speech and physiotherapy) for the duration of the study.
RESULTS:
All patients completed the stimulation protocol. Adverse events were rare. Ataxia severity improved in the verum group only.
CONCLUSION:
The combination of transcranial magnetic stimulation and classic symptomatic therapy is feasible in a neuro-rehabilitation setting and potentially ameliorates ataxia severity.
Bostan,A. C., Strick,P. L. (2018). The basal ganglia and the cerebellum: Nodes in an integrated network. Nature Reviews. Neuroscience, 19(6), 338–350. https://doi.org/10.1038/s41583-018-0002-7.
2.
Bronstein,A. M., Mossman,S [S.], Luxon,L. M. (1991). The neck-eye reflex in patients with reduced vestibular and optokinetic function. Brain : A Journal of Neurology, 114(Pt 1A), 1–11. https://pubmed.ncbi.nlm.nih.gov/1998877/.
3.
Caligiore,D., Arbib,M. A., Miall,R. C., Baldassarre,G. (2019). The super-learning hypothesis: Integrating learning processes across cortex, cerebellum and basal ganglia. Neuroscience and Biobehavioral Reviews, 100, 19–34. https://doi.org/10.1016/j.neubiorev.2019.02.008.
4.
Chen,X.-Y., Lian,Y.-H., Liu,X.-H., Sikandar,A., Li,M.-C., Xu,H.-L., Hu,J.-P., Chen,Q.-L., Gan,S.-R. (2022). Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3 . Frontiers in Aging Neuroscience, 14, 827993. https://doi.org/10.3389/fnagi.2022.827993.
5.
Cole,E. J., Stimpson,K. H., Bentzley,B. S., Gulser,M., Cherian,K., Tischler,C., Nejad,R., Pankow,H., Choi,E., Aaron,H., Espil,F. M., Pannu,J., Xiao,X., Duvio,D., Solvason,H. B., Hawkins,J., Guerra,A., Jo,B., Raj,K. S.,... Williams,N. R. (2020). Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. The American Journal of Psychiatry, 177(8), 716–726. https://doi.org/10.1176/appi.ajp.2019.19070720.
6.
Cortese,A., Simone,R., Sullivan,R., Vandrovcova,J., Tariq,H., Yau,W. Y., Humphrey,J., Jaunmuktane,Z., Sivakumar,P., Polke,J., Ilyas,M., Tribollet,E., Tomaselli,P. J., Devigili,G., Callegari,I., Versino,M., Salpietro,V., Efthymiou,S., Kaski,D.,... Houlden,H. (2019). Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nature Genetics, 51(4), 649–658. https://doi.org/10.1038/s41588-019-0372-4.
7.
Cortese,A., Tozza,S., Yau,W. Y., Rossi,S [Salvatore], Beecroft,S. J., Jaunmuktane,Z., Dyer,Z., Ravenscroft,G., Lamont,P. J., Mossman,S [Stuart], Chancellor,A., Maisonobe,T., Pereon,Y., Cauquil,C., Colnaghi,S., Mallucci,G., Curro,R., Tomaselli,P. J., Thomas-Black,G.,... Reilly,M. M. (2020). Cerebellar ataxia, neuropathy, vestibular areflexia syndrome due to RFC1 repeat expansion. Brain: A Journal of Neurology, 143(2), 480–490. https://doi.org/10.1093/brain/awz418.
8.
FrançaC., Andrade,D. C., de, Silva,V., Galhardoni,R., Barbosa,E. R., Teixeira,M. J., Cury,R. G. (2020). Effects of cerebellar transcranial magnetic stimulation on ataxias: A randomized trial. Parkinsonism & Related Disorders, 80, 1–6. https://doi.org/10.1016/j.parkreldis.2020.09.001.
9.
Gong,C., Long,Y., Peng,X.-M., Hu,H., Chen,J., Xiao,L., Zhong,Y.-B., Wang,M.-Y., Luo,Y. (2023). Efficacy and safety of noninvasive brain stimulation for patients with cerebellar ataxia: A systematic review and meta-analysis of randomized controlled trials. Journal of Neurology, 270(10), 4782–4799. https://doi.org/10.1007/s00415-023-11799-8.
10.
Hall,C. D., Herdman,S. J., Whitney,S. L., Cass,S. P., Clendaniel,R. A., Fife,T. D., Furman,J. M., Getchius,T. S. D., Goebel,J. A., Shepard,N. T., Woodhouse,S. N. (2016). Vestibular Rehabilitation for Peripheral Vestibular Hypofunction: An Evidence-Based Clinical Practice Guideline: From THE AMERICAN PHYSICAL THERAPY ASSOCIATION NEUROLOGY SECTION. Journal of Neurologic Physical Therapy: JNPT, 40(2), 124–155. https://doi.org/10.1097/NPT.0000000000000120.
11.
Hartelt,E., Scherbaum,R., Kinkel,M., Gold,R., Muhlack,S., Tönges,L. (2020). Parkinson’s Disease Multimodal Complex Treatment (PD-MCT): Analysis of Therapeutic Effects and Predictors for Improvement. Journal of Clinical Medicine, 9(6). https://doi.org/10.3390/jcm9061874.
12.
Hurtado-Puerto,A. M., Nestor,K., Eldaief,M., Camprodon,J. A. (2020). Safety Considerations for Cerebellar Theta Burst Stimulation. Clinical Therapeutics, 42(7), 1169–1190.e1. https://doi.org/10.1016/j.clinthera.2020.06.001.
13.
Ilg,W., Brötz,D., Burkard,S., Giese,M. A., Schöls,L [Ludger], Synofzik,M. (2010). Long-term effects of coordinative training in degenerative cerebellar disease. Movement Disorders25(13), 2239–2246. https://doi.org/10.1002/mds.23222.
14.
Lefaucheur,J.-P., Aleman,A., Baeken,C., Benninger,D. H., Brunelin,J., Di Lazzaro,V., Filipović,S. R., Grefkes,C., Hasan,A., Hummel,F. C., Jääskeläinen,S. K., Langguth,B., Leocani,L., Londero,A., Nardone,R., Nguyen,J.-P., Nyffeler,T., Oliveira-Maia,A. J, Oliviero,A.,... Ziemann,U. (2020) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018) . Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology, 131(2), 474–528. https://doi.org/10.1016/j.clinph.2019.11.002.
Manor,B., Greenstein,P. E., Davila-Perez,P., Wakefield,S., Zhou,J., Pascual-Leone,A. (2019). Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia: A Pilot Randomized Controlled Trial. Frontiers in Neurology, 10, 73. https://doi.org/10.3389/fneur.2019.00073.
17.
Manto,M., Argyropoulos,G. P. D., Bocci,T., Celnik,P. A., Corben,L. A., Guidetti,M., Koch,G., Priori,A., Rothwell,J. C., Sadnicka,A., Spampinato,D., Ugawa,Y., Wessel,M. J., Ferrucci,R. (2022). Consensus Paper: Novel Directions and Next Steps of Non-invasive Brain Stimulation of the Cerebellum in Health and Disease. Cerebellum (London, England), 21(6), 1092–1122. https://doi.org/10.1007/s12311-021-01344-6.
18.
Manto,M., Bower,J. M., Conforto,A. B., Delgado-García,J.M., Da Guarda,S. N. F., Gerwig,M., Habas,C., Hagura,N., Ivry,R.B., Mariën,P., Molinari,M., Naito,E., Nowak,D. A., Oulad BenTaib,N., Pelisson,D., Tesche,C. D., Tilikete,C., Timmann,D. (2012). Consensus paper: Roles of the cerebellum in motor control–the diversity of ideas on cerebellar involvement inmovement. Cerebellum (London, England), 11(2), 457–487. https://doi.org/10.1007/s12311-011-0331-9.
19.
Navari,E., Cerchiai,N., Casani,A. P. (2018). Assessment of Vestibulo-ocular Reflex Gain and Catch-up Saccades During Vestibular Rehabilitation. Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 39(10), e1111–e1117. https://doi.org/10.1097/MAO.0000000000002032.
20.
Neggers,S. F. W., Langerak,T. R., Schutter,D. J. L. G., Mandl,R. C. W., Ramsey,N. F., Lemmens,P. J. J., Postma,A. (2004). A stereotactic method for image-guided transcranial magnetic stimulation validated with fMRI and motor-evoked potentials. NeuroImage, 21(4), 1805–1817. https://doi.org/10.1016/j.neuroimage.2003.12.006.
21.
Scherbaum,R., Hartelt,E., Kinkel,M., Gold,R., Muhlack,S., Tönges,L. (2020). Parkinson’s Disease Multimodal Complex Treatment improves motor symptoms, depression and quality of life. Journal of Neurology, 267(4), 954–965. https://doi.org/10.1007/s00415-019-09657-7.
22.
Schmahmann,J. D., Sherman,J. C. (1998). The cerebellar cognitive affective syndrome. Brain : A Journal of Neurology, 121(Pt 4), 561–579. https://doi.org/10.1093/brain/121.4.561.
23.
Schmitz-Hübsch,T., Du Montcel,S. T., Baliko,L., Berciano,J., Boesch,S., Depondt,C., Giunti,P [P.], Globas,C, Infante,J[J.], Kang,J.-S, Kremer,B., Mariotti,C., Melegh,B., Pandolfo,M., Rakowicz,M., Ribai,P., Rola,R., Schöls,L [L.], Szymanski,S.,... Fancellu,R. (2006). Scale for the assessment and rating of ataxia: Development of a new clinical scale. Neurology, 66(11), 1717–1720. https://doi.org/10.1212/01.wnl.0000219042.60538.92.
24.
Shi,Y., Zou,G., Chen,Z., Wan,L., Peng,L., Peng,H., Shen,L., Xia,K., Qiu,R., Tang,B., Jiang,H. (2023). Efficacy of cerebellar transcranial magnetic stimulation in spinocerebellar ataxia type 3: A randomized, single-blinded, controlled trial. Journal of Neurology, 1–8. https://doi.org/10.1007/s00415-023-11848-2.
25.
Sikandar,A., Liu,X.-H., Xu,H.-L., Li,Y., Lin,Y.-Q., Chen,X.-Y., Li,G.-H., Lin,M.-T., Wang,N., Chen,W.-J., Ni,G.-X., Gan,S.-R. (2023). Short-term efficacy of repetitive transcranial magnetic stimulation in SCA3: A prospective, randomized, double-blind, sham-controlled study. Parkinsonism & Related Disorders, 106, 105236. https://doi.org/10.1016/j.parkreldis.2022.105236.
26.
Smółka,W., Smółka,K., Markowski,J., Pilch,J., Piotrowska-Seweryn,A., Zwierzchowska,A. (2020). The efficacy ofvestibular rehabilitation in patients with chronic unilateral vestibular dysfunction. International Journal of Occupational Medicine and Environmental Health, 33(3), 273–282. https://doi.org/10.13075/ijomeh.1896.01330.
27.
Szmulewicz,D. J., Waterston,J. A., Halmagyi,G. M., Mossman,S [S.], Chancellor,A. M., McLean,C. A., Storey,E. (2011). Sensory neuropathy as part of the cerebellar ataxia neuropathy vestibular areflexia syndrome. Neurology, 76(22), 1903–1910. https://doi.org/10.1212/WNL.0b013e31821d746e.
28.
Traschütz,A., Cortese,A., Reich,S., Dominik,N., Faber,J., Jacobi,H., Hartmann,A. M., Rujescu,D., Montaut,S., Echaniz-Laguna,A., Erer,S., Schütz,V. C., Tarnutzer,A. A., Sturm,M., Haack,T. B., Vaucamps-Diedhiou,N., Puccio,H., Schöls,L [Ludger], Klockgether,T [Thomas], Synofzik,M. (2021). Natural History, Phenotypic Spectrum, and Discriminative Features of Multisystemic RFC1 Disease. Neurology, 96(9), e1369–e1382. https://doi.org/10.1212/WNL.0000000000011528.
29.
Wang,Y [Ying], DiZhang, Wang,J., Ma,J., Lu,L., Jin,S. (2023). Effects of transcranial magnetic stimulation on cerebellar ataxia: A systematic review and meta-analysis. Frontiers in Neurology, 14, 1049813. https://doi.org/10.3389/fneur.2023.1049813.
30.
Zhou,M., Qiu,M., Jin,Y., Li,D., Tao,C., Lou,D., Hu,Z., Wang,Y [Yuchen], You,Z., Shao,Y., Zhu,Y., Qu,M., Lu,X. (2023). Effectiveness of High-Frequency Repetitive Transcranial Magnetic Stimulation in Patients With Spinocerebellar Ataxia Type 3. The Journal of ECT. Advance online publication. https://doi.org/10.1097/YCT.0000000000000925.
