Highlights
- •We reviewed the crude risk of seizures and other adverse events of rTMS in patients with epilepsy.
- •A crude per-subject risk of 2.9% (95% CI: 1.3–4.5) was estimated for seizures occurring during or shortly after.
- •The safety of rTMS applied to patients with epilepsy appears to be the same as in other conditions.
Abstract
Approximately one-third of patients with epilepsy remain with pharmacologically intractable
seizures. An emerging therapeutic modality for seizure suppression is repetitive transcranial
magnetic stimulation (rTMS). Despite being considered a safe technique, rTMS carries
the risk of inducing seizures, among other milder adverse events, and thus, its safety
in the population with epilepsy should be continuously assessed. We performed an updated
systematic review on the safety and tolerability of rTMS in patients with epilepsy,
similar to a previous report published in 2007 (Bae EH, Schrader LM, Machii K, Alonso-Alonso
M, Riviello JJ, Pascual-Leone A, Rotenberg A. Safety and tolerability of repetitive
transcranial magnetic stimulation in patients with epilepsy: a review of the literature.
Epilepsy Behav. 2007; 10 (4): 521–8), and estimated the risk of seizures and other
adverse events during or shortly after rTMS application. We searched the literature
for reports of rTMS being applied on patients with epilepsy, with no time or language
restrictions, and obtained studies published from January 1990 to August 2015. A total
of 46 publications were identified, of which 16 were new studies published after the
previous safety review of 2007. We noted the total number of subjects with epilepsy
undergoing rTMS, medication usage, incidence of adverse events, and rTMS protocol
parameters: frequency, intensity, total number of stimuli, train duration, intertrain
intervals, coil type, and stimulation site. Our main data analysis included separate
calculations for crude per subject risk of seizure and other adverse events, as well
as risk per 1000 stimuli. We also performed an exploratory, secondary analysis on
the risk of seizure and other adverse events according to the type of coil used (figure-of-8
or circular), stimulation frequency (≤1 Hz or >1 Hz), pulse intensity in terms of motor threshold (<100% or ≥100%), and number of stimuli per session (<500 or ≥ 500). Presence or absence of adverse events was reported in 40 studies (n = 426 subjects). A total of 78 (18.3%) subjects reported adverse events, of which 85%
were mild. Headache or dizziness was the most common one, occurring in 8.9%. We found
a crude per subject seizure risk of 2.9% (95% CI: 1.3–4.5), given that 12 subjects
reported seizures out of 410 subjects included in the analysis after data of patients
with epilepsia partialis continua or status epilepticus were excluded from the estimate.
Only one of the reported seizures was considered atypical in terms of the clinical
characteristics of the patients' baseline seizures. The atypical seizure happened
during high-frequency rTMS with maximum stimulator output for speech arrest, clinically
arising from the region of stimulation. Although we estimated a larger crude per subject
seizure risk compared with the previous safety review, the corresponding confidence
intervals contained both risks. Furthermore, the exclusive case of atypical seizure
was the same as reported in the previous report. We conclude that the risk of seizure
induction in patients with epilepsy undergoing rTMS is small and that the risk of
other adverse events is similar to that of rTMS applied to other conditions and to
healthy subjects. Our results should be interpreted with caution, given the need for
adjusted analysis controlling for potential confounders, such as baseline seizure
frequency. The similarity between the safety profiles of rTMS applied to the population
with epilepsy and to individuals without epilepsy supports further investigation of
rTMS as a therapy for seizure suppression.
Keywords
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Article Info
Publication History
Published online: March 09, 2016
Accepted:
January 15,
2016
Received in revised form:
January 13,
2016
Received:
December 3,
2015
Identification
Copyright
© 2016 Published by Elsevier Inc.
