Safety study of 50 Hz repetitive transcranial magnetic stimulation in patients with Parkinson's disease

David H. Benninger, Mikhail Lomarev, Eric M. Wassermann, Grisel Lopez, Elise Houdayer, Rebecca E. Fasano, Nguyet Dang, Mark Hallett

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective: Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating Parkinson's disease (PD), but the best values for rTMS parameters are not established. Fifty Hertz rTMS may be superior to ≤ 25 Hz rTMS investigated so far. The objective of this study was to determine if 50 Hz rTMS could be delivered safely in PD patients since current safety limits are exceeded. Methods: Fifty Hertz rTMS was applied with a circular coil on the primary motor cortex (M1). Stimulation intensity was first tested at 60% rest motor threshold [RMT] and 0.5 s train duration and then increased in 0.5 s steps to 2 s, and by 10% steps to 90% RMT. Multi-channel electromyography (EMG) was recorded to control for signs of increasing time-locked EMG activity including correlates of the spread of excitation and after-discharges, or an increase of M1 excitability. Pre- and post-50 Hz rTMS assessments included EEG, Unified Parkinson Disease Rating Scale (UPDRS), Grooved Pegboard Test, Serial Reaction Time Task (SRTT), Folstein Mini-Mental Status Examination (MMSE) and Verbal Fluency to control for motor and cognitive side effects. Results: Ten PD patients were investigated. Multi-channel EMG showed no signs of increased time-locked EMG activity including correlates of the spread of excitation and after-discharges, or increased M1 excitability in 9 patients. A PD patient with bi-temporal spikes in the pre-testing EEG had clinical and EMG correlates of spread of excitation at 90% RMT, but no seizure activity. Pre- and post-50 Hz assessment showed no changes. No adverse events were observed. Fifty Hertz rTMS was well tolerated except by 1 patient who wished to terminate the study due to facial muscle stimulation. Conclusion: Fifty Hertz rTMS at an intensity of 90% RMT for 2 s appears safe in patients with PD, but caution should be taken for patients with paroxysmal EEG activity. For this reason, comprehensive screening should include EEG before higher-frequency rTMS is applied. Significance: This is the first study to investigate safety of 50 Hz rTMS in humans.

Original languageEnglish
Pages (from-to)809-815
Number of pages7
JournalClinical Neurophysiology
Volume120
Issue number4
DOIs
Publication statusPublished - Apr 2009

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Transcranial Magnetic Stimulation
Parkinson Disease
Safety
Electromyography
Electroencephalography
Facial Muscles
Motor Cortex
Seizures

Keywords

  • 50 Hz rTMS
  • Parkinson's disease
  • Repetitive transcranial magnetic stimulation (rTMS)
  • Safety study

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Physiology (medical)
  • Sensory Systems

Cite this

Benninger, D. H., Lomarev, M., Wassermann, E. M., Lopez, G., Houdayer, E., Fasano, R. E., ... Hallett, M. (2009). Safety study of 50 Hz repetitive transcranial magnetic stimulation in patients with Parkinson's disease. Clinical Neurophysiology, 120(4), 809-815. https://doi.org/10.1016/j.clinph.2009.01.012

Safety study of 50 Hz repetitive transcranial magnetic stimulation in patients with Parkinson's disease. / Benninger, David H.; Lomarev, Mikhail; Wassermann, Eric M.; Lopez, Grisel; Houdayer, Elise; Fasano, Rebecca E.; Dang, Nguyet; Hallett, Mark.

In: Clinical Neurophysiology, Vol. 120, No. 4, 04.2009, p. 809-815.

Research output: Contribution to journalArticle

Benninger, DH, Lomarev, M, Wassermann, EM, Lopez, G, Houdayer, E, Fasano, RE, Dang, N & Hallett, M 2009, 'Safety study of 50 Hz repetitive transcranial magnetic stimulation in patients with Parkinson's disease', Clinical Neurophysiology, vol. 120, no. 4, pp. 809-815. https://doi.org/10.1016/j.clinph.2009.01.012
Benninger, David H. ; Lomarev, Mikhail ; Wassermann, Eric M. ; Lopez, Grisel ; Houdayer, Elise ; Fasano, Rebecca E. ; Dang, Nguyet ; Hallett, Mark. / Safety study of 50 Hz repetitive transcranial magnetic stimulation in patients with Parkinson's disease. In: Clinical Neurophysiology. 2009 ; Vol. 120, No. 4. pp. 809-815.
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abstract = "Objective: Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating Parkinson's disease (PD), but the best values for rTMS parameters are not established. Fifty Hertz rTMS may be superior to ≤ 25 Hz rTMS investigated so far. The objective of this study was to determine if 50 Hz rTMS could be delivered safely in PD patients since current safety limits are exceeded. Methods: Fifty Hertz rTMS was applied with a circular coil on the primary motor cortex (M1). Stimulation intensity was first tested at 60{\%} rest motor threshold [RMT] and 0.5 s train duration and then increased in 0.5 s steps to 2 s, and by 10{\%} steps to 90{\%} RMT. Multi-channel electromyography (EMG) was recorded to control for signs of increasing time-locked EMG activity including correlates of the spread of excitation and after-discharges, or an increase of M1 excitability. Pre- and post-50 Hz rTMS assessments included EEG, Unified Parkinson Disease Rating Scale (UPDRS), Grooved Pegboard Test, Serial Reaction Time Task (SRTT), Folstein Mini-Mental Status Examination (MMSE) and Verbal Fluency to control for motor and cognitive side effects. Results: Ten PD patients were investigated. Multi-channel EMG showed no signs of increased time-locked EMG activity including correlates of the spread of excitation and after-discharges, or increased M1 excitability in 9 patients. A PD patient with bi-temporal spikes in the pre-testing EEG had clinical and EMG correlates of spread of excitation at 90{\%} RMT, but no seizure activity. Pre- and post-50 Hz assessment showed no changes. No adverse events were observed. Fifty Hertz rTMS was well tolerated except by 1 patient who wished to terminate the study due to facial muscle stimulation. Conclusion: Fifty Hertz rTMS at an intensity of 90{\%} RMT for 2 s appears safe in patients with PD, but caution should be taken for patients with paroxysmal EEG activity. For this reason, comprehensive screening should include EEG before higher-frequency rTMS is applied. Significance: This is the first study to investigate safety of 50 Hz rTMS in humans.",
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