Motor Threshold, Medication, and Safety in Transcranial Magnetic Stimulation
A 29-year-old is enrolled in a research protocol measuring motor evoked potentials from the right first dorsal interosseous with single-pulse transcranial magnetic stimulation. She takes 40 mg of citalopram daily and 400 mg of carbamazepine twice daily for epilepsy that has been seizure-free for 6 years. She had one febrile seizure as a toddler. Resting motor threshold is being established with a figure-of-eight coil over the left motor cortex. She reports a mild headache after the first 30 stimuli and asks to continue.
1. Assess her risk profile for TMS-induced seizure and state what must happen before stimulation continues.
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Risk factors present:
- Epilepsy history (even if seizure-free for 6 years) is a relative contraindication and raises risk.
- Carbamazepine lowers the seizure threshold and is a recognized risk-increasing medication; citalopram at 40 mg is also serotonergic and can lower threshold in some patients.
- Febrile seizure in childhood is a minor additional historical factor.
- Single-pulse TMS at motor threshold is lower risk than repetitive TMS, but the combination above still warrants caution.
Before continuing: the responsible physician must review the medication list and the seizure history, the protocol's safety checklist must be completed, and a documented risk-benefit decision made. Practical measures include confirming the patient has slept and eaten, avoiding caffeine excess, keeping stimulus intensity at the minimum needed to determine threshold, spacing stimuli, and having a written seizure-management plan and trained staff present. The headache should be assessed; if it is more than a mild transient tension headache, pause and reassess. Continuing without physician sign-off would be inappropriate.
2. How should the resting motor threshold be determined, and what would you do if no response is obtained at 80% of maximum stimulator output?
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Determination: with the coil tangentially over the left motor cortex, oriented to induce current in the optimal posterior-to-anterior direction, find the hotspot for the right first dorsal interosseous, then use the relative-frequency or up-down method: the threshold is the lowest intensity at which a motor evoked potential of at least 50 microvolts peak-to-peak is elicited in roughly half of trials (commonly 5 of 10). Keep coil position and orientation constant, monitor EMG for background activity, and have the subject relaxed.
If no response at 80% of maximum output: do not simply keep escalating. First check technical factors - coil orientation, hotspot location, coil cable, EMG electrode placement and gain, and whether the subject is voluntarily contracting (facilitation lowers threshold). Re-examine for a structural reason (skull thickness, prior surgery) and confirm the device is functioning and calibrated. If a response still cannot be obtained, document the failure, do not exceed the protocol's maximum intensity, and consult the supervising physician. Repeated high-intensity stimulation in a patient with epilepsy risk without a response is not justified.