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Year : 2022  |  Volume : 1  |  Issue : 4  |  Page : 179-180

Priming coupled with low-frequency repetitive transcranial magnetic stimulation in the management of migraine: a case study

Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Submission23-Nov-2021
Date of Decision05-Dec-2022
Date of Acceptance08-Dec-2022
Date of Web Publication30-Dec-2022

Correspondence Address:
Sujita Kumar Kar
Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2773-2398.365028

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How to cite this article:
Kar SK, Choudhary P, Boda A. Priming coupled with low-frequency repetitive transcranial magnetic stimulation in the management of migraine: a case study. Brain Netw Modulation 2022;1:179-80

How to cite this URL:
Kar SK, Choudhary P, Boda A. Priming coupled with low-frequency repetitive transcranial magnetic stimulation in the management of migraine: a case study. Brain Netw Modulation [serial online] 2022 [cited 2023 Dec 2];1:179-80. Available from: http://www.bnmjournal.com/text.asp?2022/1/4/179/365028

Migraine is a debilitating condition that often runs a chronic course and may become refractory to the conventional treatment regimen (Headache Classification Committee of the International Headache Society (IHS), 2013). Both immediate and long-term pharmacological treatments are recommended for migraine. Lifestyle modification and dietary precautions are important strategies for preventing migraine. Neuromodulation techniques like transcranial magnetic stimulation (TMS) are found to be effective in the management of migraine (Hammad et al., 2021; Fernandes et al., 2022; Saltychev and Juhola, 2022). There is evidence from electrophysiological studies that occipital cortex activity is particularly altered during the ictal and pre-ictal phases of migraines (Aurora et al., 1998). A wave of cortical spreading depression is thought to propagate from the occipital visual cortex and cause the distinctive aura of migraines (Hansen et al., 2013). Migraine can originate from either the brain's peripheral or central nervous systems or both, according to research conducted on animal models (Andreou et al., 2012). With the advent of user-friendly devices and positive tolerability profiles (Miller and Matharu, 2017), non-invasive neuromodulation methods have gained traction as viable alternatives to medicines in the treatment of migraine. Compared to sham stimulation, repetitive TMS (rTMS) appears to reduce the intensity of migraine pain and the frequency of migraine attacks in people with chronic migraine. On average, rTMS reduced the number of days a person experienced pain each month by eight; however, its effect on pain intensity was likely clinically insignificant (Saltychev and Juhola, 2022). Portable TMS devices were approved in 2013 for the management of migraine. Over 5 days, patients received rTMS treatment. Two trains of 500 pulses were delivered at 1 Hz across the vertex using a repetitive magnetic stimulator, with a 1-minute break between trains. The apex was stimulated using a magnetic stimulator located at the coil’s pivot point in a figure-of-eight pattern. After receiving rTMS, patients reported a significant decrease in migraine symptoms, including pain severity, frequency and length of attacks, disability scores, and the number of tablets used to stop an attack (Hammad et al., 2021). Here, we describe a case of migraine with hypothyroidism, obesity and hypertension treated with rTMS.

A 50-year-old female diagnosed with migraine with hypothyroidism, hypertension and obesity, was hospitalized due to the persistence of her headache despite adequate trials of pharmacotherapy. Her problems started at the age of 35 years. She had episodes of headaches that start from the right hemicranial region and then spread to the entire head. Headache was severe in intensity and throbbing in character associated with anxiety, dizziness, and tremors and followed by generalized weakness. Headache was aggravated by sound and light it occurs almost daily over the past few years. Headache lasted 8 to 10 hours and could be relieved by analgesics and vomiting. Headache exacerbated during seasonal weather changes and sleep deprivation. There was significant distress experienced by the patient due to these symptoms. She has been treated with propranolol (up to 40 mg/d), topiramate (up to 100 mg/d), flunarizine (up to 10 mg/d) and amitriptyline (up to 25 mg/d) for an adequate period (alone and in various combinations) over the past 5 years with treatment adherence. She was also taking Olmesartan 40 mg/d for hypertension and levothyroxine 100 μg/d for hypothyroidism. Along with these medications, the patient was also taking milnacipran 25 mg/d, escitalopram up to 10 mg/d and naproxen 500 mg as and when required in combination with domperidone and ergotamine 1 mg/d and paracetamol 250 mg/d. However, the improvement was insignificant. She also complained of sadness of mood (mostly during the headache) which she attributed to headaches and anxiety during and before the attack. Her sleep was disturbed, appetite was adequate, and personal hygiene and self-care were appropriate as per her socioeconomic status; however, she was facing difficulties in completing daily household chores and fulfilling her role in the family due to the severity and debilitating nature of her illness. The patient was normotensive and euthyroid on medications and her blood investigation revealed free T4 levels of 1.5 ng/dL and thyroid-stimulating hormone levels of 1.1 μIU/mL. Her family history, personal history and premorbid personality were insignificant. Detailed physical and neurological examination was done and the results were within normal limits. Her body mass index was 35.8 kg/m2. She was diagnosed with migraine with aura, accompanied by hypothyroidism, hypertension and obesity. Due to the nonimprovement of her headache, rTMS therapy was initiated as an adjuvant treatment to ongoing pharmacotherapy (topiramate 100 mg/d, amitriptyline 25 mg/d and a combination of propranolol 40 mg/d and flunarizine 10 mg/d). The baseline score on the Visual Analog Scale was 8/10. She was given rTMS over the vertex area with 1200 pulses/session (600 pulses for priming and 600 pulses for the active low-frequency session) at 100% resting motor threshold (which was identified to be 66%) over a period of 4 weeks at a frequency of one session daily. Priming of the vertex was done at a frequency of 6 Hz, with 60 pulses/train and an inter-train interval of 30 seconds for 10 trains (total 600 pulses), which was subsequently followed by 600 pulses of low-frequency rTMS (1 Hz, 60 pulses/train, 10 trains, an inter-train interval of 5 seconds). A total of 20 sessions were delivered. At the end of 4 weeks, the pain severity was reduced from 8/10 to 1/10 on the Visual Analog Scale score. Additionally, her requirement for analgesics was significantly reduced. The frequency of migraine attacks was also reduced to 1 - 2 episodes per week of short duration.

There was complete resolution in her secondary depressive and anxiety symptoms too. The patient did not report any adverse effects during or after the rTMS therapy. Evidence suggest that high-frequency rTMS applied to the primary motor cortex (M1) can reduce pain and other symptoms associated with neuropathic pain, fibromyalgia, and migraine (Lefaucheur et al., 2020). Stimulation sessions have been demonstrated to be well tolerated and manageable, with the added benefit of extending the benefits of daily stimulation sessions through scheduled maintenance sessions (Fernandes et al., 2022). As hyperexcitability of the cortex is seen in patients with migraine, low-frequency rTMS on the hyperexcitable cortex have beneficial effects in the management of migraine (Hammad et al., 2021). In this study, we adopted this concept by priming the cortex before low-frequency rTMS. Evidence suggests that priming with 6 Hz rTMS enhances the effectiveness of subsequent low-frequency rTMS in various neuropsychiatric disorders (Iyer et al., 2003; Fitzgerald et al., 2008). We did not find any literature regarding the use of priming prior to low-frequency rTMS in the management of migraine. This is the first case study that reveals the safety and effectiveness of priming coupled with low-frequency rTMS in the management of migraine. Clinicians may consider priming coulped with low-frequency rTMS in the treatment of refractory migraine.

We have obtained written informed consent from each patient.[11]

Open access statement: This is an open access journal, and articles are distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms

  References Top

Andreou AP, Sprenger T, Goadsby PJ (2012) Cortical spreading depression-evoked discharges on trigeminothalamic neurons. Headache 52:900.  Back to cited text no. 1
Aurora SK, Ahmad BK, Welch KM, Bhardhwaj P, Ramadan NM (1998) Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine. Neurology 50:1111-1114.  Back to cited text no. 2
Fernandes AM, Graven-Nielsen T, de Andrade DC (2022) New updates on transcranial magnetic stimulation in chronic pain. Curr Opin Support Palliat Care 16:65-70.  Back to cited text no. 3
Fitzgerald PB, Hoy K, McQueen S, Herring S, Segrave R, Been G, Kulkarni J, Daskalakis ZJ (2008) Priming stimulation enhances the effectiveness of low-frequency right prefrontal cortex transcranial magnetic stimulation in major depression. J Clin Psychopharmacol 28:5258.  Back to cited text no. 4
Hammad AB, Elsharkawy RE, Abdel Azim GS (2021) Repetitive transcranial magnetic stimulation as a prophylactic treatment in migraine. Egypt J Neurol Psychiatry Neurosurg 57:5.  Back to cited text no. 5
Hansen JM, Baca SM, Vanvalkenburgh P, Charles A (2013) Distinctive anatomical and physiological features of migraine aura revealed by 18 years of recording. Brain 136:3589-3595.  Back to cited text no. 6
Headache Classification Committee of the International Headache Society (IHS) (2013) The International Classification of Headache Disorders, 3rd ed (beta version). Cephalalgia 33:629-808.  Back to cited text no. 7
Iyer MB, Schleper N, Wassermann EM (2003) Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation. J Neurosci 23:10867-10872.  Back to cited text no. 8
Lefaucheur JP, Aleman A, Baeken C, Benninger DH, Brunelin J, Di Lazzaro V, Filipović SR, Grefkes C, Hasan A, Hummel FC, Jääskel- äinen SK, Langguth B, Leocani L, Londero A, Nardone R, Nguyen JP, Nyffeler T, Oliveira-Maia AJ, Oliviero A, Padberg F, et al. (2020) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018). Clin Neurophysiol 131:474-528.  Back to cited text no. 9
Miller S, Matharu M (2017) Non-invasive neuromodulation in primary headaches. Curr Pain Headache Rep 21:14.  Back to cited text no. 10
Saltychev M, Juhola J (2022) Effectiveness of high-frequency repetitive transcranial magnetic stimulation in migraine: a systematic review and meta-analysis. Am J Phys Med Rehabil 101:1001-1006.  Back to cited text no. 11


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