|Year : 2019 | Volume
| Issue : 2 | Page : 68-73
The possible role of repetitive transcranial magnetic stimulation in dysphagia following brain stem infarctions
EISayed A.M Tageldin, Mohamed K.M Khalil, Wafik S Bahnasy, Basem H Fouda
Neurology, Neuropsychiatry Department, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||08-May-2018|
|Date of Acceptance||20-Aug-2019|
|Date of Web Publication||18-May-2020|
MD Wafik S Bahnasy
Neurology, Neuropsychiatry Department, Faculty of Medicine, Tanta University, ReyadGhoraba Street, Tanta, 31527
Background Dysphagia is a very common manifestation of brain stem infarctions, which is usually severe enough to need special feeding programs including nasogastric tube application. Repetitive transcranial magnetic stimulation (rTMS) can modulate the cortical excitability and enhance the recovery of swallowing dysfunctions.
Aim To evaluate the possible therapeutic role of rTMS in accelerating recovery of dysphagia following brain stem infarctions.
Patients and methods This study was conducted on 30 dysphagic patients following brain stem infarctions; 15 received real rTMS and 15 received sham rTMS on bilateral supratentorial cortical swallowing areas. Every patient underwent 10 rTMS sessions repeated five times per week for 2 successive weeks. Scheduled dysphagia severity was evaluated using The Dysphagia Outcome and Severity Scale at stroke onset, after the first rTMS session, and then at 7, 30, and 60 days after the last rTMS session (visits 0, 1, 2, 3, and 4, respectively).
Results There was significant improvement of dysphagia in patients who received real rTMS compared with those who received sham rTMS during visits 1 and 2. The improvement was maintained through visits 3 and 4, but without significant difference.
Conclusion Bilateral application of real rTMS on cortical swallowing areas for patients with dysphagia following brain stem infarctions has a potential rapid maintained improving effect of swallowing functions with decreased burden of aspiration in the early poststroke period until recovery takes place.
Keywords: brain stem infarction, dysphagia, repetitive transcranial magnetic stimulation
|How to cite this article:|
Tageldin EA, Khalil MK, Bahnasy WS, Fouda BH. The possible role of repetitive transcranial magnetic stimulation in dysphagia following brain stem infarctions. Tanta Med J 2019;47:68-73
|How to cite this URL:|
Tageldin EA, Khalil MK, Bahnasy WS, Fouda BH. The possible role of repetitive transcranial magnetic stimulation in dysphagia following brain stem infarctions. Tanta Med J [serial online] 2019 [cited 2021 Mar 1];47:68-73. Available from: http://www.tdj.eg.net/text.asp?2019/47/2/68/284495
| Introduction|| |
Ischemic stroke is defined as an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarctions . Despite the great advances in acute stroke management, it still represents the second cause of death worldwide and one of the commonest causes of prolonged disabilities .
Dysphagia is a common poststroke manifestation, affecting 37–78% of stroke cases in general and 94% in patients with brain stem infarctions . The presence of dysphagia increases the global burden of stroke with prolonged hospital stay, poorer long-term outcome, and higher mortality rate owing to aspiration pneumonia, malnutrition, dehydration, and risks associated with enteral feeding . Most patients with poststroke dysphagia show satisfactory spontaneous improvement within 1–2 months, but recovery may be delayed in some exceptional severe cases . Dysphagia following brain stem infarctions is usually oro-pharyngeal type owing to impairment in the mouth and tongue sensory functions, prolongation of the transit time needed for triggering the pharyngeal swallowing reflexes, laryngeal elevation, glottic closure, and cricopharyngeal relaxation .
The swallowing muscles are asymmetrically bilaterally represented in both precentral cortices, and dominance of the cortical swallowing centers is independent on handedness. Repetitive TMS may improve the swallowing functions with faster recovery of dysphagia either owing to compensatory reorganization or restoration of the cortical projections to the brain stem swallowing centers .
| Aim|| |
The aim of this study was to assess the possible therapeutic role of repetitive transcranial magnetic stimulation (rTMS) in accelerating recovery of dysphagia following brain stem infarctions.
| Patients and methods|| |
This study was conducted on 30 consecutive dysphagic patients following brain stem infarctions attending the Neurovascular Unit and ICUs of the Neurology Department and The Center of Neurology and Psychiatry, Tanta University Hospitals, in a 6-month period started in June 2016. The included patients were divided into two groups; group I included 15 patients who received real rTMS, and group II included 15 patients who received sham rTMS as a control group. The included patients were fully conscious adult patients with first-ever brain stem infarction. This was a randomized controlled study using a consecutive alternating method for randomization.
Exclusion criteria included patients with hemorrhagic stroke, recurrent or severe stroke [National Institute of Health Stroke Scale (NIHSS>22)], epilepsy, heavy smokers, chronic chest patients, and those older than 70 years. Patients with disturbed consciousness, which deteriorated during their ICU stay, or needed assisted ventilation and patients with rTMS contraindications were also excluded, including epileptic patients, patients with prosthetic valves, patients with cardiac pacemakers, patients with arterial stenting, and those with metallic material as joint replacement and internal orthopedic fixations.
Brain stem infarctions were diagnosed clinically and radiologically using noncontrast brain computed tomography and/or MRI scans of different sequences, including diffusion-weighted images. Dysphagia was diagnosed according to the three stages of Standardized Swallowing Assessment  and its degree was assessed using The Dysphagia Outcome and Severity Scale (DOSS) .
The device used for rTMS was Magstim Rapid2 with second-generation double 70-mm coil stimulators produced in UK by Magstim Company Ltd (Carmarthenshire Wales, UK). The motor evoked potentials of the first dorsal interosseous or abductor pollicis brevis muscles were recorded using an electromyography device Medelec Synergy N2 EMG Monitoring System (Oxford Instruments Medical, Old Working, UK). The motor threshold was determined by repeated magnetic stimulation of the motor area and is defined as the minimum TMS intensity required to elicit motor evoked potentials of more than 50 µV peak-to-peak amplitude in at least 50% of successive trials, in resting or slightly contracted targeted muscles.
The stimulation sites were the swallowing areas in the premotor cortices of both hemispheres, which are located 3 cm lateral and 6 cm anterior to the vertex (the point of intersection between the line from the frontal and occipital protuberances and the right and left tragus) ,. Patients were instructed to remove all magnetically sensitive objects such as metallic keys, credit cards, mobiles, watches, hearing aids, and laptops before sessions.
All included patients received bilateral 10 rTMS sessions repeated five times per week for 2 successive weeks. Ten trains of real rTMS were done per session in bilateral sequential manner. Each train was 120% of the motor threshold intensity, 3-Hz frequency, and 10-s duration, with 50 s inter-train intervals. The total number of pulses in each session was 300 (3 Hz×10 s×10 trains) pulses in each side. For sham rTMS, the same technique was done as real rTMS, but the coil was angled 90° by lifting the lateral aspect of coil which delivers a very small proportion of the dose (<25%) . The rTMS safety followed the guidelines by Rossi et al. , including exclusion of epileptics and avoidance of very high frequency or rTMS intensity more than 130% of motor threshold.
The study protocol was approved by The Research Ethics Committee and Quality Assurance Unit, Faculty of Medicine, Tanta University. Participation was voluntary, and all participants received detailed information concerning the aims of the study and the possible risks of rTMS work, and an informed consent was obtained from all before commencement of the study.
Patients’ dysphagia severities were early assessed using the DOSS at stroke onset and after the first rTMS session, and then they were reevaluated in follow-up visits at 7, 30, and 60 days after the last rTMS session (visits 0, 1, 2, 3, and 4, respectively). Stroke severity was assessed at the onset and followed up till the last session of rTMS using the NIHSS. The degree of disability was assessed at visits 2 and 3 using the Modified Rankin Scale .
One patient in group I developed focal seizure in the third rTMS session and decided to discontinue the study, leading to inclusion of another case. During follow-up, two patients in group II died within 1 month after discharge: one owing to myocardial infarction and the other experienced sudden arrest. The data of the two patients were included in the statistics of visits 0, 1, and 2, but they were eliminated from those of visits 3 and 4.
Statistical analysis was conducted using statistical package for the social studies (SPSS), version 19 created by IBM (Illinois, Chicago, USA). For numerical values, the range and mean±SD were calculated and analyzed by the unpaired Student t-test, χ2-test, and analysis of variance tests. P value less than 0.05 was considered statistically significant.
| Results|| |
The study showed that there were nonsignificant differences between groups I and II regarding the ages, severity of stroke measured by NIHSS, severity of dysphagia measured by DOSS, and duration from stroke onset till the first session of rTMS (days) (57.47±7.68, 16.87±1.77, 3.33±1.54, and 4.33±1.75 in group I versus 55.60±10.24, 16.93±1.71, 3.53±1.64, and 4.16±1.17 in group II, with P=0.576, 0.925, 0.733, and 0.756, respectively). Regarding the motor threshold intensities, there were nonsignificant differences between both the groups in the first rTMS session (50.60±6.27 in group I vs. 48.90±6.67 in group II, with P=0.478), but in the last 10th session, the motor threshold intensities were significantly lower in group I compared with group II (43.23±4.12 vs. 47.53±6.31 with P=0.013; [Table 1]).
|Table 1 Stroke and dysphagia severities at the onset and transcranial magnetic stimulation data of patients who received real (group I) versus patients who received sham repetitive transcranial magnetic stimulation (group II)|
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The study demonstrated nonsignificant difference between both groups regarding the common stroke risks including sex distribution, diabetes, smoking, and dyslipidemia ([Table 2]). Regarding the sites of infarctions, there was nonsignificant difference between both studied groups. Group I had six cases with pontomedullary and nine medullary infarctions. On the contrary, group II had eight cases with pontomedullary and seven medullary infarctions ([Figure 1]).
|Table 2 Sex and stroke risk distribution in patients who received real (group I) versus patients who received sham repetitive transcranial magnetic stimulation (group II)|
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|Figure 1 MRI of a 61-year-old studied patient who had brain stem infarction.|
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On the contrary, the study displayed significant improvement of dysphagia severity measured by the DOSS in group I, which received real rTMS, after the first session of real rTMS compared with that at stroke onset (P=0.0098). This improvement persisted till the next evaluation made 7 days after the last session (visit 3) (P=0.0033; [Table 3]). On the contrary, group II showed nonsignificant difference in dysphagia severity in visits 1 and 2 when compared with that measured in visit 0 (P=0.972 and 0.877, respectively; [Table 3]).
|Table 3 The dysphagia outcome and severity scale in patients who received real (group I) versus patients who received sham repetitive transcranial magnetic stimulation (group II)|
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In addition to the previous results, comparing both groups regarding dysphagia severity at the consecutive visits of follow-up exhibited initial nonsignificant difference in visit 0, but swallowing enhancement in group I after real rTMS made the DOSS significantly improved in group I compared with group II in visits 1 and 2 (P=0.049 and 0.048, respectively). On the contrary, long-term follow-up of DOSS showed nonsignificant differences between both groups in visits 3 and 4 (P=0.901 and 0.902, respectively; [Table 4]).
|Table 4 Comparison between patients who received real (group I) and patients who received sham repetitive transcranial magnetic stimulation (group II) regarding dysphagia, stroke, and disability severities|
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The study showed nonsignificant differences between both groups regarding stroke severity measured by the NIHSS in visits 1 and 2 (P=0.829 and 0.680). At the same time, late follow-up of patients’ degree of disability measured by Modified Rankin Scale showed nonsignificant difference between both studied groups (P=0.933 and 0.784, respectively; [Table 4]).
| Discussion|| |
Cerebrovascular stroke is one of the major cause of deaths and prolonged disabilities worldwide . Dysphagia is a common brain stem infarction manifestation, and its rapid recovery is of paramount importance to improve the amount and variety of ingested food and minimize aspiration, which prolongs morbidity and hospital stay . Current dysphagia management methods are of limited values, with high incidence of aspiration, including posture training, dietary modifications, swallowing exercises, drug therapy, oral muscles electrical stimulation and botulinum toxin injection .
This work studied the probable role of real rTMS in enhancing recovery of dysphagia following brain stem infarctions. This was dependent on the anticipation that supratentorial facilitation of the cortical swallowing areas via the cortical projections to the brain stem centers may lead to fast and potentially long-lasting improvement of the swallowing function.
The study included 30 patients with brain stem infarctions, with mean age of 56.7±9.41 years and equal male to female ratio. These results are different from that of Kolukısa et al. , who reported higher mean age of patients with posterior circulation infarction (65.3±1.22 years) and higher male to female ratio. These differences were possibly owing to inclusion of only large artery posterior circulation infarctions and exclusion of lacunar in their study. This study reported 6.7% death rate among patients with brain stem infarctions within the first 1.5 months after stroke, which is also lower than that of Kolukısa et al. , perhaps owing to shorter duration of follow-up and exclusion of disturbed conscious patients in this study.
The study showed that 10 sessions of bilaterally applied real rTMS on the supratentorial cortical swallowing areas over 2 weeks period caused improvement of swallowing functions in the early poststroke period after brain stem infarctions until spontaneous recovery takes place later. This beneficial effect of rTMS can improve patient’s nutrition and reduce the risk of aspiration. These results agreed with that of Michou et al. , who reported improvement of brain stem poststroke dysphagia after application of rTMS and attributed this to the facilitation of the swallowing brain stem centers by supratentorial cortical stimulation.
The study showed immediate improvement of dysphagia following the first real rTMS session, denoting fast effect of magnetic stimulation. This rapid effect is crucial in early poststroke period for rapid patients’ recovery and avoidance of morbid complications and poor outcome. These results are in accordance with the review article of Doeltgen et al. , who conducted a meta-analysis on 17 online studies and concluded that noninvasive magnetic brain stimulation provides a useful adjunctive tool in poststroke swallowing rehabilitation. Chervyakov et al.  attributed the rapid action of TMS to its enhancement and facilitation of different neurotransmitters, notably dopamine.
The study also showed observed decline in the intensity of motor thresholds in successive real rTMS sessions without similar outcome in those receiving sham rTMS, pointing to substantial modulation and enhancement of the cortical excitability by real rTMS. These results are in agreement with that of Cabib et al.  and Macrae et al. , who proposed that increased excitability induced by real rTMS may promote neuroplasticity and long-term potentiation of brain stem swallowing centers with consequent prolonged dysphagia improvement.The study showed that the improvements in dysphagia severity and activity of daily living are still maintained in patients who received bilateral real rTMS stimulation in 1- and 2-month follow-up visits, which points to the beneficial effect of rTMS in management of dysphagia in the early poststroke period till spontaneous regression of symptoms take place. These results are in agreement with the work of Khedr and Abo-Elfetoh  who documented maintained improvements of dysphagia and activity of daily living in 1 and 2 months of follow-up in brain stem dysphagic patients who received rTMS.
| Conclusion|| |
The study concluded that early bilateral application of real rTMS on both cortical swallowing areas for patients with brain stem infarctions accelerates dysphagia improvement and decreases the burden of aspiration in the early poststroke period till spontaneous improvement takes place within 1–2 months.
The study needed to be a double-blind placebo-control study, which needs specially designed coils producing acoustic artifacts, so that the operator and examiner cannot determine which patients took active or sham sessions, but unfortunately, these special coils were unavailable. At the same time, the complexity of the swallowing process narrows the spectrum of the DOSS, making recording of trivial improvements in dysphagia non-applicable.
Financial support and sponsorship
Conflicts of interest
All authors declare that there were no financial or non-financial competing interests related to the study.
| References|| |
Sacco RL, Kasner SE, Broderick JP, Caplan Culebras A, Elkind MSV, George MG et al.
An Updated Definition of Stroke for the 21st Century A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44:2064–2089.
Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA et al.
Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet 2014; 383:245–254.
Wang Z, Song WQ, Wang L. Application of noninvasive brain stimulation for post-stroke dysphagia rehabilitation. Kaohsiung J Med Sci 2017; 33:55–61.
Takizawa C, Gemmell E, Kenworthy J, Speyer R. Systematic review of the prevalence of oropharyngeal dysphagia in stroke, Parkinson’s disease, Alzheimer’s disease, head injury, and pneumonia. Dysphagia 2016; 31:434–441.
Cohen DL, Roffe C, Beavan J, Blackett B, Fairfield CA, Hamdy S et al.
Post-stroke dysphagia: a review and design considerations for future trials. Int J Stroke 2016; 11:399–411.
Martino R, Terrault N, Ezerzer F, Mikulis D, Diamant NE. Dysphagia in a patient with lateral medullary syndrome: insight into the central control of swallowing. Gastroenterology 2001; 121:420–426.
Teismann I, Sonja S, Tobias W, Olaf S, Maren F, Agnes F et al.
Cortical swallowing processing in early subacute stroke. BMC Neurol 2011; 11:34–47.
Lee KM, Kim HJ. Practical assessment of dysphagia in stroke patients. Ann Rehabil Med 2015; 39:1018–1027.
O’Neil KH, Purdy M, Falk J, Gallo L. The dysphagia outcome and severity scale. Dysphagia 1999; 14:139–145.
Kobayashi M, Fujimaki T, Mihara B, Ohira T. Repetitive transcranial magnetic stimulation once a week induces sustainable long-term relief of central post-stroke pain. Neuromodulation 2015; 18:249–254.
Khedr EM, Abo-Elfetoh N. Therapeutic role of rTMS on recovery of dysphagia in patients with lateral medullary syndrome and brainstem infarction. J Neurol Neurosurg Psychiatry 2010; 81:495–499.
Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH et al.
Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 2014; 125:2150–2206.
Rossi S, Hallett M, Rossini PM, Pascual-Leone A. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009; 120:2008–2039.
Fearon P, McArthur KS, Garrity K, Graham LJ, Mc-Groarty G, Vincent S et al.
Pre-stroke modified rankin stroke scale has moderate interobserver reliability and validity in an acute stroke setting. Stroke 2012; 43:3184–3188.
Hankey GJ. Stroke. Lancet 2017; 389:641–654.
Lin T, Jiang L, Dou Z, Wu C, Liu F, Xu G et al.
Effects of theta burst stimulation on suprahyoid motor cortex excitability in healthy subjects. Brain Stimul 2017; 10:91–98.
Yang SN, Pyun SB, Kim HJ, Ahn HS, Rhyu BJ. Effectiveness of non-invasive brain stimulation in dysphagia subsequent to stroke: a systemic review and meta-analysis. Dysphagia 2015; 30:383–391.
Kolukısa M, Gültekin TO, Baran GE, Aralasmak A, Kocaman G, Gürsoy AE et al.
One-year follow-up in patients with brainstem infarction due to large-artery atherothrombosis. Neuropsychiatr Dis Treat 2015; 11:379–384.
Michou E, Mistry S, Jefferson S, Tyrrell P, Hamdy S. Characterizing the mechanisms of central and peripheral forms of neurostimulation in chronic dysphagic stroke patients. Brain Stimul 2014; 7:66–73.
Doeltgen SH, Bradnam LV, Young JA, Fong E. Transcranial non-invasive brain stimulation in swallowing rehabilitation following stroke: a review of the literature. Physiol Behav 2015; 143:1–9.
Chervyakov AV, Chernyavsky AY, Sinitsyn DO, Piradov MA. Possible mechanisms underlying the therapeutic effects of transcranial magnetic stimulation. Front Hum Neurosci 2015; 9:303.
Cabib C, Ortega O, Vilardell N, Mundet L, Clave P, Rofes L. Chronic post-stroke oropharyngeal dysphagia is associated with impaired cortical activation to pharyngeal sensory inputs. Eur J Neurol 2017; 24:1355–1362.
Macrae PR, Jones RD, Huckabee ML. The effect of swallowing treatments on corticobulbar excitability: a review of transcranial magnetic stimulation induced motor evoked potentials. J Neurosci Methods 2014; 233:89–98.
[Table 1], [Table 2], [Table 3], [Table 4]