Transcranial Magnetic Stimulation: New Treatment for Acute Migraine with Aura? Stay Tuned
Abstract & Commentary
By Dara Jamieson, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Jamieson reports she is a retained consultant for Boehringer Ingelheim, Merck, and Ortho-McNeil, and is on the speaker's bureau for Boehringer Ingelheim and Merck.
Synopsis: Transcranial magnetic stimulation resulted in improvement in pain-free headache response rates after 2, 24 and 48 hours, as compared to sham stimulation, in patients with acute migraine with aura.
Sources: Lipton RB, et. al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: A randomised, double-blind, parallel-group, sham-controlled trial. Lancet Neurol 2010;9:373-380. Epub 2010 Mar 4.
Diener HC. Single-pulse transcranial magnetic stimulation: A new way to treat migraine attacks with aura. Lancet Neurol 2010;9:335-337. Epub 2010 Mar 4.
Recent use of transcranial magnetic stimulation in depression has led to its evaluation in other disorders of the brain, including migraine. Transcranial magnetic stimulation is a non-invasive technique using a coil of electrical current to apply a pu
lsed magnetic field to the scalp and cortex, altering neuronal firing. Cortical spreading depression, with a posterior to anterior wave of cortical excitation then inhibition, is a pathophysiological correlate to the initiation of migraine with aura and is a logical target for this technique. This paper reports on an industry-sponsored, randomized, double-blind, parallel-group, two-phase, sham-controlled, multi-center study of single-pulse transcranial magnetic stimulation (sTMS) used to treat an acute attack of migraine with aura. The study of the efficacy and safety of the device was in two parts. There were initially 267 adults with the International Headache Society criteria for migraine with visual aura who were evaluated for their ability to keep a headache diary and recognize the onset of a migraine with aura. In phase two, 201 patients, who were able to comply with the diary and treatment protocol, were randomly allocated by computer to either sham stimulation (n=99) or sTMS (n=102). Participants were instructed to treat up to three attacks over three months while experiencing the migraine aura. Preventative, but not abortive, medications were allowed during the trial. The primary outcome was pain-free response two hours after the first attack, and co-primary outcomes were non-inferiority at two hours for migraine accompanying symptoms of nausea, photophobia, and phonophobia. For the 164 patients who treated at least one attack with sTMS (n=82) or sham stimulation (n=82; modified intention-to-treat analysis set), pain-free response rates after two hours were significantly higher with sTMS (32/82 [39%]) than with sham stimulation (18/82 [22%]), for a therapeutic gain of 17% (95% CI 3-31%; p=0.0179). Sustained pain-free response rates significantly favored sTMS at 24 hours and 48 hours post-treatment. Non-inferiority was shown for nausea, photophobia, and phonophobia. No device-related serious adverse events were recorded, and incidence and severity of adverse events were similar between the sTMS and sham groups.
Early treatment of migraine with aura by sTMS resulted in increased freedom from pain at two hours compared with sham stimulation, and absence of pain was sustained for up to two days after treatment. The encouraging results of this sTMS study indicate a promising acute treatment for patients with migraine with aura. The use of sTMS for treatment of acute migraine with aura has teleological appeal, as there appears to be a cogent explanation for its effect. This study addresses the major concern of a device trial by using a sham device; but, the stimulation doses and the optimal treatment protocol still need to be determined. Interesting, the commonly noted phenomenon of enhanced efficacy of acute abortive treatment in patients on preventative medication was noted by patients who used the sTMS. As encouraging as these results may be, the majority of migraineurs experience migraine without aura. Cortical spreading depression may also play a role in migraine without aura, expanding the possible use of sTMS; however, timing of initiation of treatment may be problematic without an aura to indicate the migraine headache onset.
In the accompanying editorial, Hans-Christoph Diener, MD pointed out that some research questions are still unanswered and more studies, including a head-to-head comparison with triptans, need to be done. He pointed out the lack of benefit in some secondary endpoints, such as decrease in headache pain from severe-moderate pain to mild-no pain at two hours. However, the results of this well designed trial are encouraging for the millions of migraine sufferers and more investigation is needed.