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 Table of Contents  
REVIEW ARTICLE
Year : 2016  |  Volume : 22  |  Issue : 2  |  Page : 77-80

Repetitive transcranial magnetic stimulation: Review of the novel technique for the treatment of tinnitus


Department of Otorhinolaryngology, Faculty of Clinical Sciences, College of Health Sciences, Aminu Kano Teaching Hospital, Bayero University, Kano, Nigeria

Date of Web Publication11-May-2016

Correspondence Address:
Abdulazeez O Ahmed
P. O. Box: 14529, Main Post Office, Kano
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-7749.182286

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  Abstract 

Tinnitus remains a huge burden worldwide. It is said to affect one third of persons at some point in their lives. Various therapeutic approaches have been tried without a seemingly appreciable result. This article reviews the role of repetitive transcranial magnetic stimulation (rTMS) as a novel method of treating patients with tinnitus. To review the literature on rTMS in the management of tinnitus. Literature search using a systematic review of available databases such as PubMed, EMBASE, Cochrane library, Web of science and Science Direct was used. The efficacy of this new method of treating tinnitus is yet to be fully documented. Long-term effects such as induction of metaplastic change, genetic mutation from the magnetic fields surrounding the underlying tissues are all possible. To improve and strengthen acceptability in its efficacy, some of these adverse effects have to be adequately controlled.

Keywords: Magnetic stimulation, Review, Tinnitus, Transcranial, Treatment


How to cite this article:
Ahmed AO. Repetitive transcranial magnetic stimulation: Review of the novel technique for the treatment of tinnitus. Indian J Otol 2016;22:77-80

How to cite this URL:
Ahmed AO. Repetitive transcranial magnetic stimulation: Review of the novel technique for the treatment of tinnitus. Indian J Otol [serial online] 2016 [cited 2019 Nov 21];22:77-80. Available from: http://www.indianjotol.org/text.asp?2016/22/2/77/182286


  Introduction Top


Tinnitus is defined as the perception of sound in the absence of acoustic stimulation. It is a huge burden all over the world and from the United States, it is estimated to affect about 34.25 million people, and affects approximately one-third of adults at some point in their lives, and up to 15% seek medical treatment for on-going symptoms.[1] Data for developing countries are however scarce and where available validity is an issue. Out of desperation for a permanent solution, sufferers of tinnitus are reaching out for treatments with repetitive transcranial magnetic stimulation (rTMS) including but not limited to Nigerians that can afford it. The causes of tinnitus can be said to be protean and sometimes ominous.[2] Tinnitus can be subjective (tinnitus can only be heard by the patient) or objective (it can be heard by the examiner with or without the aid of a stethoscope), but for the purpose of brevity, emphasis would dwell more on the treatment of subjective tinnitus. Since medieval times treatments such as inserting electrodes into the ear, use of local concoctions, herbs to even orthodox medicines such as vitamins, labyrinthine vasodilators (betaserc, cinnarizine, etc.) to counseling, local anesthetic injections, hypnosis,[3] and use of cognitive behavioral therapy, white noise generators, tinnitus maskers, and occasionally, in those with accompanying hearing impairment, the use of hearing aids to reduce threshold by amplification of sounds have been employed.


  Background Information Top


TMS is a novel technique for the treatment of tinnitus which is gradually gaining popularity among researchers worldwide.[4],[5] It works on the simple principle of inductance to get electrical energy across the scalp and tinnitus being associated with increased neuronal excitability in the auditory cortex requires a noninvasive, safe, and painless technique to modify/induce electric currents in localized cortical regions. While modulating the brain activity levels according to settings of the electromagnetic coil such as frequency, number of pulses, train and regime duration with intertrain intervals.[6]

TMS works via a capacitor discharged through an insulated wire coil held against the scalp generating a small magnetic field which creates a weak electric current under the skull thereby causing depolarization and generating action potentials in those neurons which reach firing thresholds.[7] When applied at subthreshold intensities, rTMS affects intracortical networks and also the excitability of the cortex.[8] To reduce response of the cortex to synaptic inputs and suppress cortical excitability, rTMS is delivered at 1 Hz for 20 min (range 1–20 Hz). Similarly, human cortical excitability is facilitated by rTMS at higher frequencies.


  Methods Top


Literature search on the current treatments of tinnitus in local and international journals was reviewed. To ensure maximum literature was obtained, online sources such as Medline, PubMed, EMBASE, CINAHL, Cochrane library, Scopus, Biomed central, Web of science and Science Direct, with restriction to articles in English were used. Using search string such as tinnitus AND transcranial magnetic stimulation AND noninvasive; tinnitus AND treatments AND transmagnetic stimulation.


  Contraindications Top


Similar to magnetic resonance imaging (MRI) which uses magnetic fields, TMS uses the same principles. Therefore, shares almost same contraindications such as cardiac pacemaker, intracranial metallic implants and eye implants, serious heart disease, increased intracranial pressure, plus a history of seizure attacks. Exceptions may be made in circumstances where the physical properties of the metal object are known, and there is a need to perform rTMS. Furthermore, cochlear implant is not included in this list because it can actually be used to deliver external electric stimulation to suppress tinnitus. This was exemplified by a study in which a unilaterally deafened cochlear implant subject had his tinnitus completely suppressed by a low-rate (<10 Hz) stimulus, delivered at a level softer than tinnitus to the apical part of the cochlea.[9]


  Adverse Effects Top


Furthermore, there are other potential adverse effects of TMS that have been documented.[10] These are mood changes effects, cognition, seizures, headaches, burns from scalp electrodes, psychological consequences of induced seizures and transient effects on lymphocytes, hormones, and auditory threshold shift. Speculations also show that there are theoretical adverse effects such as histotoxicity, kindling (process occurring in animals wherein the repeated administration of an initially subconvulsive stimulus results in progressive intensification of induced neuroelectrical activity, culminating in a seizure), long-term potentiation and long-term depression, and social consequences of induced seizure. Some of these effects were not however documented with use in tinnitus management, probably due to a lower dose use, but they must be kept in view. According to a recent systematic review, no severe effects, such as epileptic seizures, were reported in rTMS treatment of patients so far.[11]

Considering all the above-mentioned effects, ethical issues will have to be addressed promptly during patient selection such as informed consent, the potential benefits must be seen to outweigh the risks via an independent assessment and finally there should be equal distribution of the burden and benefits of the research or treatment protocol as well.


  Discussion Top


Careful patient selection and treatment planning has been shown to produce favorable outcomes such as patients with short duration tinnitus or mild degree of tinnitus usually do better than patients with chronic tinnitus. In a recent study, data were analyzed from 538 patients with chronic tinnitus receiving either low-frequency rTMS over the left temporal cortex (n = 345, 1 Hz, 110% motor threshold, 2000 stimuli/day) or combined temporal and frontal stimulation (n = 193, 110% motor threshold, 2000 stimuli at 20 Hz over left dorsolateral prefrontal cortex plus 2000 stimuli at 1 Hz over temporal cortex).[12] Both stimulation protocols resulted in a significant decrease of tinnitus questionnaire (TQ) scores; however, effect sizes were small. They concluded that rTMS shows only small but clinically significant effects in the treatment of chronic tinnitus.[13] Furthermore, recent preclinical data in healthy controls have suggested that the effects of low-frequency rTMS can be enhanced by dopaminergic drugs, using dopamine reuptake inhibitor bupropion, 18 subjects were evaluated over 3 months. For the whole sample, there was a significant effect of rTMS treatment over time. However, there were no significant differences between the bupropion and the control group; therefore, they also concluded dopaminergic inhibitor drugs do not enhance the effect of rTMS in the treatment of chronic tinnitus.[14]


  Outcomes Top


The laterality of symptoms and the type and/or nature of tinnitus plays a significant role in the outcome of treatment planning, i.e. patients that present with unilateral tinnitus respond better to rTMS than patients with bilateral tinnitus.[15] Similarly, patients with low-frequency pure tone tinnitus respond better at 1 Hz rTMS whereas patients with white noise tinnitus are said to respond best to short bursts of higher frequency (>10 Hz) rTMS. Several doses of rTMS are usually required to achieve good results because single dose effect is usually short-lived; as a result, most treatment protocols deliver stimulations for 5 days/week and up to 7 days to 2 weeks. These treatment effects are said to last for up to 6 months to 1 year.[16] To add credence to this, a recent study investigated predictors for treatment response and duration of treatment effects in 235 patients with chronic tinnitus treated with TMS, they discovered that at the end of the follow-up period assessments showed 2.12 years and 3.9 years for responders and nonresponders, respectively (response criterion was defined as an improvement of at least ten points in the TQ score between baseline and the follow-up assessment 90 days after treatment).[17] This study shows an even longer effect period when compared to other studies.[16],[18]

With regard to laterality, one study reported on TMS treatments in 114 patients with unilateral tinnitus using TMS aimed at the contralateral auditory cortex.[19] They however excluded bilateral tinnitus in their criteria (patients presenting with same frequency and intensity in both ears) and patients with a history of seizure were also excluded. Stimulations were repeated at 1, 5, 10, and 20 Hz at 200 pulses. At the end of this study, it was concluded that TMS of the auditory cortex can temporarily ameliorate or even suppress tinnitus in certain subgroups of unilateral tinnitus sufferers. However, we still cannot say why bilateral sufferers were excluded per se; after all, the group treatment intensity may not entirely be homogenous even for the unilateral sufferers allowing for high interindividual variability in treatment effects. Albeit to say, this is a small study and a large-scale randomized clinical trials is required to effectively conclude on laterality of tinnitus in patient selection.

Similarly, controversy also exists as to which side should be stimulated. Is it the left side or the side contralateral to the side of perceived tinnitus? An attempt to answer this question was postulated in based on positron emission tomography studies that there was always increased metabolism in the left auditory cortex irrespective of the side of tinnitus, and that left-sided rTMS can suppress this metabolic activity.[20] On the other hand, functional MRI and magnetoencephalography studies suggest the neural generator might be located contralaterally to the tinnitus side, the authors then concluded rTMS contralateral to the side of the tinnitus has a greater beneficial effect on symptoms than ipsilateral rTMS and better suppression than left-sided stimulation. These results were however obtained by nonplacebo-controlled stimulations.

To maintain suppression of tinnitus symptom, a study reported the case of 15-year history of disabling tinnitus in a 44-year-old male in whom three follow-up treatments produced an impressive reduction in his tinnitus symptoms, and this was eventually sustained for 6 months afterward.[21] Therefore, it suffices to say that a maintenance dose may be required in the long term to suppress tinnitus with TMS.


  Conclusion Top


Putting all the above into perspective, one will now begin to imagine what possible effect such therapy will have on these subjects/patients in the long term such as induction of metaplastic change, genetic mutation due to chronic irritation/or fall-out effect from the magnetic fields created between the scalp and its underlying tissues which are constantly firing-off action potentials, can we equally infer with full confidence that TMS alone can promote reorganization and normalization of the auditory cortical excitability and tonotopicity? Several speculations about the efficacy of this new method of treating tinnitus are yet to be fully elucidated, such as from a genetic point of view, can variations in genes that encode for brain-derived neurotrophic factor, alter the cortical response to rTMS? Using such unphysiologic means to suppress cortical excitability, what is the homeostatic response and if at all there is, how does hyperpolarization of brain neurons impact on achieved success and how about brain cell fatigue?

Some studies have tried to potentiate the effect of TMS using drugs that act on neurotransmitters such as dopaminergic drugs, gamma-aminobutyric acid agonist, and selective serotonin – reuptake inhibitors to influence the cortical response to rTMS.[22] To strengthen clinical trials, future work will have to try to answer some of the aforementioned questions and help formulate guidelines for rTMS in tinnitus management. It suffices to say, therefore, that patient's whose tinnitus is of short duration and with less severity are the best candidates for rTMS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Heller AJ. Classification and epidemiology of tinnitus. Otolaryngol Clin North Am 2003;36:239-48.  Back to cited text no. 1
    
2.
Conlin AE, Massoud E, Versnick E. Tinnitus: Identifying the ominous causes. CMAJ 2011;183:2125-8.  Back to cited text no. 2
    
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Cheung SW, Larson PS. Tinnitus modulation by deep brain stimulation in locus of caudate neurons (area LC). Neuroscience 2010;169:1768-78.  Back to cited text no. 3
    
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Hoare DJ, Kowalkowski VL, Kang S, Hall DA. Systematic review and meta-analyses of randomized controlled trials examining tinnitus management. Laryngoscope 2011;121:1555-64.  Back to cited text no. 5
    
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Garin P, Gilain C, Van Damme JP, de Fays K, Jamart J, Ossemann M, et al. Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation. J Neurol 2011;258:1940-8.  Back to cited text no. 8
    
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Zeng FG, Tang Q, Dimitrijevic A, Starr A, Larky J, Blevins NH. Tinnitus suppression by low-rate electric stimulation and its electrophysiological mechanisms. Hear Res 2011;277:61-6.  Back to cited text no. 9
    
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Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: Report and suggested guidelines from the international workshop on the safety of repetitive transcranial magnetic stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol 1998;108:1-16.  Back to cited text no. 10
    
11.
Meng Z, Liu S, Zheng Y, Phillips JS. Repetitive transcranial magnetic stimulation for tinnitus. Cochrane Database Syst Rev 2011;(10):CD007946.  Back to cited text no. 11
    
12.
Lehner A, Schecklmann M, Landgrebe M, Kreuzer PM, Poeppl TB, Frank E, et al. Predictors for rTMS response in chronic tinnitus. Front Syst Neurosci 2012;6:11.  Back to cited text no. 12
    
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Frank E, Schecklmann M, Landgrebe M, Burger J, Kreuzer P, Poeppl TB, et al. Treatment of chronic tinnitus with repeated sessions of prefrontal transcranial direct current stimulation: Outcomes from an open-label pilot study. J Neurol 2012;259:327-33.  Back to cited text no. 13
    
14.
Kleinjung T, Steffens T, Landgrebe M, Vielsmeier V, Frank E, Burger J, et al. Repetitive transcranial magnetic stimulation for tinnitus treatment: No enhancement by the dopamine and noradrenaline reuptake inhibitor bupropion. Brain Stimul 2011;4:65-70.  Back to cited text no. 14
    
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Stinear CM. Tinnitus management with repetitive transcranial magnetic stimulation. N Z Med J 2010;123:73-6.  Back to cited text no. 15
    
16.
Khedr EM, Abo-Elfetoh N, Rothwell JC, El-Atar A, Sayed E, Khalifa H. Contralateral versus ipsilateral rTMS of temporoparietal cortex for the treatment of chronic unilateral tinnitus: Comparative study. Eur J Neurol 2010;17:976-83.  Back to cited text no. 16
    
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Burger J, Frank E, Kreuzer P, Kleinjung T, Vielsmeier V, Landgrebe M, et al. Transcranial magnetic stimulation for the treatment of tinnitus: 4-year follow-up in treatment responders – A retrospective analysis. Brain Stimul 2011;4:222-7.  Back to cited text no. 17
    
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wChung HK, Tsai CH, Lin YC, Chen JM, Tsou YA, Wang CY, et al. Effectiveness of theta-burst repetitive transcranial magnetic stimulation for treating chronic tinnitus. Audiol Neurootol 2012;17:112-20.  Back to cited text no. 18
    
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De Ridder D, Verstraeten E, Van der Kelen K, De Mulder G, Sunaert S, Verlooy J, et al. Transcranial magnetic stimulation for tinnitus: Influence of tinnitus duration on stimulation parameter choice and maximal tinnitus suppression. Otol Neurotol 2005;26:616-9.  Back to cited text no. 19
    
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De Ridder D. Should rTMS for tinnitus be performed left-sided, ipsilaterally or contralaterally, and is it a treatment or merely investigational? Eur J Neurol 2010;17:891-2.  Back to cited text no. 20
[PUBMED]    
21.
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22.
Ziemann U. TMS induced plasticity in human cortex. Rev Neurosci 2004;15:253-66.  Back to cited text no. 22
    



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Abstract
Introduction
Background Infor...
Methods
Contraindications
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