The Impact of Stimulation Parameters on Cardiovascular Outcomes in Chronic Stroke Patients Following Transcranial Direct Current Stimulation—A Pilot Controlled, Randomized, Double-Blind Crossover Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Design
2.2. Ethical Aspects
2.3. Eligibility Criteria
2.4. Sample Recruitment and Selection
2.5. Transcranial Direct Current Stimulation
2.6. Assessments
2.7. Heart Rate Variability
2.8. Functional Capacity Assessment
2.9. Sample Size
2.10. Randomization
2.11. Statistical Analysis
3. Results
4. Discussion
4.1. Basal Condition
4.2. After Stimulation
4.3. Effects of tDCS on the Autonomic Nervous System
4.4. Assessment Parameters
5. Limitations and Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Dorrance, A.M.; Fink, G. Effects of Stroke on the Autonomic Nervous System. Compr. Physiol. 2015, 5, 1241–1263. [Google Scholar] [CrossRef] [PubMed]
- Raphaely-Beer, N.; Katz-Leurer, M.; Soroker, N. Lesion configuration effect on stroke-related cardiac autonomic dysfunction. Brain Res. 2020, 1733, 146711. [Google Scholar] [CrossRef] [PubMed]
- Eckardt, M.; Gerlach, L.; Welter, F. Prolongation of the Frequency-Corrected QT Dispersion following Cerebral Strokes with Involvement of the Insula of Reil. Eur. Neurol. 1999, 42, 190–193. [Google Scholar] [CrossRef] [PubMed]
- Tokgözoglu, S.L.; Batur, M.K.; Topçuoglu, M.A.; Saribas, O.; Kes, S.; Oto, A. Effects of Stroke Localization on Cardiac Autonomic Balance and Sudden Death. Stroke 1999, 30, 1307–1311. [Google Scholar] [CrossRef]
- Xiong, L.; Leung, H.; Chen, X.; Leung, W.; Soo, O.; Wong, K. Autonomic dysfunction in different subtypes of post-acute ischemic stroke. J. Neurol. Sci. 2014, 337, 141–146. [Google Scholar] [CrossRef]
- Cha, K.H.; Kang, N.Y.; Huh, S.; Ko, S.-H.; Shin, Y.-I.; Min, J.H. The Effects of Autonomic Dysfunction on Functional Outcomes in Patients with Acute Stroke. Brain Sci. 2023, 13, 1694. [Google Scholar] [CrossRef]
- Meyer, S.; Strittmatter, M.; Fischer, C.; Georg, T.; Schmitz, B. Lateralization in autononic dysfunction in ischemic stroke involving the insular cortex. NeuroReport 2004, 15, 357–361. [Google Scholar] [CrossRef]
- Constantinescu, V.; Matei, D.; Ignat, B.; Hodorog, D.; Cuciureanu, D.I. Heart Rate Variability Analysis: A Useful Tool to Assess Poststroke Cardiac Dysautonomia. Neurologist 2020, 25, 49–54. [Google Scholar] [CrossRef]
- Dutsch, M.; Burger, M.; Dorfler, C.; Schwab, S.; Hilz, M.J. Cardiovascular autonomic function in poststroke patients. Neurology 2007, 69, 2249–2255. [Google Scholar] [CrossRef]
- Damkjær, M.; Simonsen, S.A.; Heiberg, A.V.; Mehlsen, J.; West, A.S.; Jennum, P.; Iversen, H.K. Autonomic dysfunction after mild acute ischemic stroke and six months after: A prospective observational cohort study. BMC Neurol. 2023, 23, 26. [Google Scholar] [CrossRef]
- Heinz, G.; De Angelis, K.; Corso, S.D.; De Sousa, M.H.G.; Viana, A.; Dos Santos, F.; Corrêa, J.C.F.; Corrêa, F.I. Effects of Transcranial Direct Current Stimulation (tDCS) and Exercises Treadmill on Autonomic Modulation of Hemiparetic Patients Due To Stroke—Clinic Test, Controlled, Randomized, Double-Blind. Front. Neurol. 2020, 10, 1402. [Google Scholar] [CrossRef] [PubMed]
- Okano, A.H.; Fontes, E.B.; Montenegro, R.A.; Farinatti, P.d.T.V.; Cyrino, E.S.; Li, L.M.; Bikson, M.; Noakes, T.D. Brain stimulation modulates the autonomic nervous system, rating of perceived exertion and performance during maximal exercise. Br. J. Sports Med. 2015, 49, 1213–1218. [Google Scholar] [CrossRef] [PubMed]
- Montenegro, R.A.; Farinatti, P.d.T.V.; Fontes, E.B.; Soares, P.P.d.S.; da Cunha, F.A.; Gurgel, J.L.; Porto, F.; Cyrino, E.S.; Okano, A.H. Transcranial direct current stimulation influences the cardiac autonomic nervous control. Neurosci. Lett. 2011, 497, 32–36. [Google Scholar] [CrossRef] [PubMed]
- Graham, H.K.; Harvey, A.; Rodda, J.; Nattrass, G.R.; Pirpiris, M. The Functional Mobility Scale (FMS). J. Pediatr. Orthop. 2004, 24, 514–520. [Google Scholar] [CrossRef] [PubMed]
- Bertolucci, P.H.; Brucki, S.M.; Campacci, S.R.; Juliano, Y. The Mini-Mental State Examination in a general population: Impact of educational status. Arq. Neuropsiquiatr. 1994, 52, 1–7. [Google Scholar] [CrossRef]
- Thair, H.; Holloway, A.L.; Newport, R.; Smith, A.D. Transcranial Direct Current Stimulation (tDCS): A Beginner’s Guide for Design and Implementation. Front. Neurosci. 2017, 11, 641. [Google Scholar] [CrossRef]
- Homan, R.W.; Herman, J.; Purdy, P. Cerebral location of international 10–20 system electrode placement. Electroencephalogr. Clin. Neurophysiol. 1987, 66, 376–382. [Google Scholar] [CrossRef]
- Borg, G.A. Psychophysical bases of perceived exertion. Med. Sci. Sports Exerc. 1982, 14, 377–381. [Google Scholar] [CrossRef]
- ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. American Thoracic Society. ATS statement: Guidelines for the six-minute walk test. Am. J. Respir. Crit. Care Med. 2002, 166, 111–117, Erratum in: Am J. Respir Crit Care Med. 2016, 193, 1185. [Google Scholar] [CrossRef]
- Yperzeele, L.; van Hooff, R.-J.; Nagels, G.; De Smedt, A.; De Keyser, J.; Brouns, R. Heart Rate Variability and Baroreceptor Sensitivity in Acute Stroke: A Systematic Review. Int. J. Stroke 2015, 10, 796–800. [Google Scholar] [CrossRef]
- Grilletti, J.V.F.; Scapini, K.B.; Bernardes, N.; Spadari, J.; Bigongiari, A.; Mazuchi, F.d.A.e.S.; Caperuto, E.C.; Sanches, I.C.; Rodrigues, B.; De Angelis, K. Impaired baroreflex sensitivity and increased systolic blood pressure variability in chronic post-ischemic stroke. Clinics 2018, 73, e253. [Google Scholar] [CrossRef] [PubMed]
- Lees, T.; Shad-Kaneez, F.; Simpson, A.M.; Nassif, N.T.; Lin, Y.; Lal, S. Heart Rate Variability as a Biomarker for Predicting Stroke, Post-stroke Complications and Functionality. Biomark. Insights 2018, 13, 1177271918786931. [Google Scholar] [CrossRef]
- Hilz, M.J.; Dütsch, M.; Perrine, K.; Nelson, P.K.; Rauhut, U.; Devinsky, O. Hemispheric influence on autonomic modulation and baroreflex sensitivity. Ann. Neurol. 2001, 49, 575–584. [Google Scholar] [CrossRef] [PubMed]
- Oppenheimer, S.M.; Gelb, A.; Girvin, J.P.; Hachinski, V.C. Cardiovascular effects of human insular cortex stimulation. Neurology 1992, 42, 1727. [Google Scholar] [CrossRef]
- Roncato, G.; da Fontoura, F.F.; Spilimbergo, F.B.; Meyer, G.M.B.; Watte, G.; de Vargas, W.O.; Casali, K.R.; Berton, D.C.; Rigatto, K. Parasympathetic modulation withdrawal improves functional capacity in pulmonary arterial hypertension. Respir. Physiol. Neurobiol. 2021, 287, 103620. [Google Scholar] [CrossRef] [PubMed]
- Ulrich-Lai, Y.M.; Herman, J.P. Neural regulation of endocrine and autonomic stress responses. Nat. Rev. Neurosci. 2009, 10, 397–409. [Google Scholar] [CrossRef] [PubMed]
- Schestatsky, P.; Simis, M.; Freeman, R.; Pascual-Leone, A.; Fregni, F. Non-invasive brain stimulation and the autonomic nervous system. Clin. Neurophysiol. 2013, 124, 1716–1728. [Google Scholar] [CrossRef]
- da Silva, F.T.G.; Browne, R.A.V.; Pinto, C.B.; Velez, F.G.S.; Egito, E.S.T.D.; Rêgo, J.T.P.D.; da Silva, M.R.; Dantas, P.M.S.; Fregni, F. Transcranial direct current stimulation in individuals with spinal cord injury: Assessment of autonomic nervous system activity. Restor. Neurol. Neurosci. 2017, 35, 159–169. [Google Scholar] [CrossRef]
- Pekny, M.; Wilhelmsson, U.; Tatlisumak, T.; Pekna, M. Astrocyte activation and reactive gliosis—A new target in stroke? Neurosci. Lett. 2018, 689, 45–55. [Google Scholar] [CrossRef]
- Buffo, A.; Rolando, C.; Ceruti, S. Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential. Biochem. Pharmacol. 2010, 79, 77–89. [Google Scholar] [CrossRef]
- Callai, E.M.M.; Zin, L.E.F.; Catarina, L.S.; Ponzoni, D.; Gonçalves, C.A.S.; Vizuete, A.F.K.; Cougo, M.C.; Boff, J.; Puricelli, E.; Fernandes, E.K.; et al. Evaluation of the immediate effects of a single transcranial direct current stimulation session on astrocyte activation, inflammatory response, and pain threshold in naïve rats. Behav. Brain Res. 2022, 428, 113880. [Google Scholar] [CrossRef] [PubMed]
- Zhang, K.-Y.; Rui, G.; Zhang, J.-P.; Guo, L.; An, G.-Z.; Lin, J.-J.; He, W.; Ding, G.-R. Cathodal tDCS exerts neuroprotective effect in rat brain after acute ischemic stroke. BMC Neurosci. 2020, 21, 1–13. [Google Scholar] [CrossRef]
- Monai, H.; Hirase, H. Astrocytic calcium activation in a mouse model of tDCS-Extended discussion. Neurogenesis 2016, 3, e1240055. [Google Scholar] [CrossRef] [PubMed]
- Burr, R.L. Interpretation of Normalized Spectral Heart Rate Variability Indices In Sleep Research: A Critical Review. Sleep 2007, 30, 913–919. [Google Scholar] [CrossRef] [PubMed]
- Shaffer, F.; McCraty, R.; Zerr, C.L. A healthy heart is not a metronome: An integrative review of the heart’s anatomy and heart rate variability. Front. Psychol. 2014, 5, 1040. [Google Scholar] [CrossRef] [PubMed]
- Pagani, M.; Montano, N.; Porta, A.; Malliani, A.; Abboud, F.M.; Birkett, C.; Somers, V.K. Relationship between spectralcomponents of cardiovascular variabilities and directmeasures of muscle sympathetic nerve activity in humans. Circulation 1997, 95, 1441–1448. [Google Scholar] [CrossRef]
- Furlan, R.; Porta, A.; Costa, F.; Tank, J.; Baker, L.; Schiavi, R.; Robertson, D.; Malliani, A.; Mosqueda-Garcia, R. Oscillatorypatterns in sympathetic neural discharge and cardiovascular variables during orthostatic stimulus. Circulation 2000, 101, 886–892. [Google Scholar] [CrossRef]
- Ko, D.-K.; Lee, H.; Kim, D.-I.; Park, Y.-M.; Kang, N. Transcranial direct current stimulation improves heart rate variability: A systematic review and meta-analysis. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2024, 134, 111072. [Google Scholar] [CrossRef]
Characteristic | Right Injury (N = 10) | Left Injury (N = 10) | p |
---|---|---|---|
Age (years) 1 | 60.3 ± 10.8 | 60.2 ± 9.6 | 0.05 |
Gender (F/M) | 10 (3/7) | 10 (5/5) | |
Ischemic stroke 2 | 7 (70%) | 6 (60%) | |
Hemorrhagic stroke 2 | 3 (30%) | 4 (40%) | |
HR (bpm) 1 | 86.6 ± 15.85 | 81.9 ± 19.85 | 0.57 |
SBP (mmHg) 1 | 125 ± 22.73 | 126 ± 15.05 | 0.90 |
DBP (mmHg) 1 | 81 ± 15.95 | 79 ± 7.38 | 0.72 |
SpO2 (%) 1 | 95 ± 1.88 | 95.1 ± 1.97 | 0.12 |
Injury time (months) 3 | 67.5 (30.7–96.5) | 40.0 (20.7–66.7) | |
B-blocker medication 2 | 4 (40%) | 9 (90%) | |
ACE inhibitor medication 2 | 3 (30%) | 1 (10%) | |
No medication 2 | 3 (30%) | 0 | |
HRV1 | |||
LF (n.u.) 1 | 69.42 ± 13.48 | 65.7 ± 15.33 | 0.57 |
HF (n.u.) 1 | 30.58 ± 13.48 | 34.30 ± 15.33 | 0.57 |
LF/HF 1 | 2.60 ± 1.71 | 2.19 ± 1.71 | 0.62 |
6MWT (m) 3 | 227.7 (125.2–292.5) | 333.5 (205–455) |
Left injury (n = 10) | ||||||
Variables | Active tDCS on T3 | Sham tDCS on T3 | ||||
Pre-treatment | Post-treatment | p-value | Pre-treatment | Post-treatment | p-value | |
6MWT (m) | 333.5 (205–455) | 364.5 (259–481) * | 0.00 | 316.5 (227.5–470.2) | 326 (228–445.2) | 0.83 |
Active tDCS on T4 | Sham tDCS on T4 | |||||
6MWT (m) | 343.5 (227.5–81.7) | 355 (261–476) | 0.50 | 338.5 (223.5–498.7) | 355 (261–476) | 0.87 |
Right injury (n = 10) | ||||||
Variables | Active tDCS on T3 | Sham tDCS on T3 | ||||
6MWT (m) | 227.7 (125.2–292.5) | 253.3 (129.2–322.5) * | 0.00 | 242 (142.5–328) | 242 (142.5–328) | 0.08 |
Active tDCS on T4 | Sham tDCS on T4 | |||||
6MWT (m) | 221 (135.5–312.2) | 253 (124–319) | 0.28 | 229 (137.2–351.2) | 238.5 (134.2–331) | 0.95 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Corrêa, F.I.; Uehara, L.; de Andrade, M.L.; da Silva, G.O.; De Angelis, K.; Viana, A.; Bertani, C.N.S.; Corrêa, J.C.F.; Fregni, F. The Impact of Stimulation Parameters on Cardiovascular Outcomes in Chronic Stroke Patients Following Transcranial Direct Current Stimulation—A Pilot Controlled, Randomized, Double-Blind Crossover Trial. Biomedicines 2024, 12, 1998. https://doi.org/10.3390/biomedicines12091998
Corrêa FI, Uehara L, de Andrade ML, da Silva GO, De Angelis K, Viana A, Bertani CNS, Corrêa JCF, Fregni F. The Impact of Stimulation Parameters on Cardiovascular Outcomes in Chronic Stroke Patients Following Transcranial Direct Current Stimulation—A Pilot Controlled, Randomized, Double-Blind Crossover Trial. Biomedicines. 2024; 12(9):1998. https://doi.org/10.3390/biomedicines12091998
Chicago/Turabian StyleCorrêa, Fernanda Ishida, Laura Uehara, Michele Lacerda de Andrade, Gustavo Oliveira da Silva, Katia De Angelis, Ariane Viana, Catarina Novaes Souza Bertani, João Carlos Ferrari Corrêa, and Felipe Fregni. 2024. "The Impact of Stimulation Parameters on Cardiovascular Outcomes in Chronic Stroke Patients Following Transcranial Direct Current Stimulation—A Pilot Controlled, Randomized, Double-Blind Crossover Trial" Biomedicines 12, no. 9: 1998. https://doi.org/10.3390/biomedicines12091998