Neuronavigation based 10 sessions of repetitive transcranial magnetic stimulation therapy in chronic migraine: an exploratory study

DOI: https://doi.org/10.1007/s10072-020-04505-3

Abstract-Summary We targeted the left motor cortex using fMRI-guided neuronavigation.

Twenty right-handed patients were randomized into real and sham rTMS group. Baseline subjective pain assessments were done using visual analog scale (VAS) and questionnaires: State-Trait Anxiety Inventory, Becks Depression Inventory, and Migraine Disability Assessment (MIDAS) questionnaire.

For corticomotor excitability parameters, resting motor thresholds and motor-

evoked potentials were mapped.

Real rTMS was administered at 70% of Resting MT. There are no studies reporting the use of fMRI-based TMS for targeting the

motor cortex in CM patients.

We observed a significant reduction in the mean VAS rating, headache frequency, and MIDAS questionnaire in real rTMS group which was maintained after 1 month of follow-up.

Ten sessions of fMRI-based rTMS over the left motor cortex may provide long- term pain relief in CM, but further studies are warranted to confirm our preliminary findings.

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Extended: Real rTMS was administered at 70% RMT using the same orientation

as for determining RMT and MEP.

We observed a significant reduction in the VAS rating for pain which was main-

tained after 1 month of follow-up.

Ten sessions of neuronavigated high-frequency repetitive transcranial magnetic stimulation of left primary motor cortex is a safe and effective therapy in decreasing chronic migraineurs’ pain and attack rate.

Introduction The mechanisms of pain relief remain unexplored accompanied by variations in the findings of sensory tests and corticomotor excitability parameters in CM patients [477, 478].

There are inadequate studies that report the efficacy of multiple-session rTMS in CM patients along with the paucity of optimal stimulation parameters for persistent analgesic effect [479, 480].

There are no studies reporting the use of fMRI-based TMS targeting the motor

cortex in CM patients.

We ventured to explore the substrate for the pain relief using neuronavigation over the left motor cortex and investigated the efficacy of 10 sessions of high-fre- quency rTMS paradigm.

Material and Methods Twenty right-handed participants (11 females, 9 males; age 33 ± 8 years, mean ± SD) diagnosed with CM (ICHD 2013 code 1.3) were recruited from Neurology Headache Clinics, AIIMS, New Delhi.

The tests for determining thermal pain thresholds (cold and hot) were first done

at the left hand (dorsum of thumb) which was the reference site in our study.

To compare the changes between real vs sham rTMS group at three different time points, i.e., baseline/pre- intervention, post-intervention, and follow-up, Mann- Whitney U or unpaired t test was used for non-parametric or parametric data, respectively.

Of the changes within the real/sham rTMS therapy group for three different time points, i.e., baseline/pre- intervention, post-intervention, and follow-up, either one- way ANOVA followed by post hoc Tukey test or Kruskal- Wallis test followed by post hoc Dunn’s test was used for parametric and non-parametric data, respectively.

Results One-way ANOVA of VAS scores for within-group comparison of Real rTMS (8.000 ± 1.33 vs 4.200 ± 2.04 vs 4.800 ± 2.25; p = 0.0003, F = 11.38) and sham rTMS group (7.70 ± 1.42 vs 6.60 ± 1.35 vs 6.70 ± 1.29, p = 0.15, F = 2.02) showed signifi- cant difference in Real rTMS group.

Tukey’s multiple comparison test revealed a significant difference between base- line vs post-intervention, and baseline vs follow-up VAS score of real rTMS group. A significant difference was observed when the comparison was done between pre-intervention vs follow-up within real rTMS (30.30 ± 30.18 vs 3.700 ± 4.001; p = 0.0157) or sham rTMS (24.50 ± 21.16 vs 13.80 ± 19.40; p = 0.0293) group with paired t test after checking for normality.

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Discussion The main finding of the present study is that ten sessions of high-frequency rTMS over the primary motor cortex attenuates pain in patients with chronic migraine and the effect is maintained for at least 1 month.

Pain relief was also reflected by the reduction in headache frequency which fur- ther decreased after follow-up, suggesting that rTMS triggered a synaptic plasticity causing reverberation in the neural circuitry which may outlast the period of active stimulation [481].

Studies targeting motor cortex rTMS for chronic pain conditions have previously reported a reduction in disability and an improvement in the quality of life [482, 483]. These studies indicate that motor cortex rTMS has a common mechanism of reducing disability both in widespread chronic pain of fibromyalgia and localized chronic pain of Chronic Regional Pain Syndrome type 1.

Possibly, high-frequency rTMS that was applied to the motor cortex increased the excitability of the anterior cingulate cortex which further activates medial thala- mus, and finally, it decreased the participant’s thermal pain threshold [484].

Conclusion As chronic migraine becomes non-responsive to medicine, rTMS can be considered as adjuvant or independent therapy for the amelioration of migraine pain and head- ache frequency.

Ten sessions of neuronavigated high-frequency repetitive transcranial magnetic stimulation of left primary motor cortex is a safe and effective therapy in decreasing chronic migraineurs’ pain and attack rate.

The lack of any effects on cortical excitability needs further exploration with the neuropharmacological bases of the analgesia which may explain the dichotomy of effects over the sensory and pain thresholds.

Acknowledgement A machine generated summary based on the work of Kumar, Anant; Mattoo, Bhawna; Bhatia, Rohit; Kumaran, Senthil; Bhatia, Renu. 2020 in Neurological Sciences.

Cortical Mechanisms of Single-Pulse Transcranial Magnetic Stimulation in Migraine