Non-Invasive Brain Stimulation Therapies Offer New Therapeutic Opportunities

This article originally appeared in the Dystonia Dialogue.

“During my fellowship training at Duke, the faces of dystonia patients with painful postures and tremors stayed with me,” said Noreen Bukhari-Parlakturk, MD, PhD, a movement disorder neurologist and clinical investigator at Duke Neurological Disorders Clinic. “Their stories of resilience and optimism—despite daily hardship and social misunderstanding—inspired me to ask the hard questions about this disease and affirmed my life mission to develop disease-modifying therapy for them.”

Dystonia can be a challenging disorder to treat. Treatment must be customized to the unique needs of each patient. For some patients, available therapies such as botulinum neurotoxin injections or deep brain stimulation can dramatically improve quality of life. For other patients, these treatments provide little to no benefit. “There is absolutely a need for novel therapies,” said Dr. Bukhari-Parlakturk. “I see it daily in my dystonia clinic where patients tell me the current combination of treatments helped ‘a little’ or ‘some.’ I am not satisfied with that.”

Transcranial Magnetic Stimulation Therapy
After years of working to advance therapies for neurological diseases, Dr. Bukhari-Parlakturk received a DMRF Clinical Fellowship in 2017. The award provided the opportunity to pursue specialized training in movement disorders and original research focused on dystonia. “It meant everything!” she explained. “The DMRF clinical fellowship support was the first time I was proposing to study dystonia and enlist the help of volunteers. It validated that my ideas about understanding the disease and developing therapy for dystonia patients will address a critical need in the field.”

Dr. Bukhari-Parlakturk is conducting research to investigate the use of transcranial magnetic stimulation therapy (TMS) to treat focal hand dystonia. TMS is a non-invasive, non-surgical technique to stimulate brain activity. Electricity is pulsed into the brain through an electromagnetic coil positioned against the head. The pulses stimulate neurons in the targeted brain region.

TMS has been used since the 1980s as a research tool to study the pathophysiology of neurological disorders, including dystonia. The use of TMS for dystonia for research paved the way for its exploration as a therapy. When used therapeutically, TMS is applied in sessions repeated over a schedule of days or weeks. Adverse effects are rare and may include seizure, fainting, and headache.

Correcting Faulty Brain Circuits
The exact mechanism of action of TMS is not fully understood. Dr. Bukhari-Parlakturk explained: “We know from prior studies that the symptoms of dystonia are due to a problem with the brain’s electrical circuit. I am interested in identifying and correcting this electrical circuit in dystonia patients using TMS. My hope is that if I target the underlying problem, I can not only provide prolonged symptom benefit but also affect the dystonia disease pathway.”

The potential of TMS for use in dystonia has been shown in a handful of studies. Several trials using low-frequency repeated TMS have shown reduction of focal hand dystonia symptoms. A pilot study demonstrated that low-frequency repeated TMS reduced muscle spasms and pain in three patients with secondary generalized dystonia. A randomized, sham-controlled, blinded study of TMS in eight cervical dystonia patients demonstrated marked benefit in seven patients, with an apparent cumulative benefit over time. In all studies, TMS was safe and well-tolerated by study volunteers.

Benefit from repeated TMS has been shown to last from days to weeks. Dr. Bukhari-Parlakturk is hoping to harness the benefits of TMS into a lasting treatment option: “I am interested in developing this technique to provide stable and prolonged relief in writer’s cramp dystonia [focal hand dystonia], so it can be a meaningful treatment option for patients.” Hand dystonia is among the most challenging focal dystonias to treat effectively. Symptoms can interfere with holding objects, writing, using utensils, keyboarding—virtually any task requiring fine motor control of the hands.

Moving Forward
TMS and additional therapeutic brain stimulation techniques may ultimately provide treatment options to dystonia patients for whom traditional therapies, such as oral medications and injected botulinum neurotoxin are not adequately effective. “There is a high pay off when we get non-invasive brain stimulation techniques to work,” said Dr. Bukhari-Parlakturk. “This is why there is such excitement to advance this technique by patients and researchers alike.”

TMS might also play a valuable role in helping to better predict which dystonia patients will respond well to deep brain stimulation (DBS).

Advancements in bringing new therapeutic technologies to market require cooperation among basic researchers in the lab, clinical researchers, biotechnology engineers who develop medical devices, and—perhaps most importantly—patients willing and able to volunteer for clinical studies. “We are moving in the right direction and our success in developing treatment options is driven by patients—by their hope and participation in the discovery process,” said Dr. Bukhari-Parlakturk. “I am grateful to the dystonia participants in my research study who have contributed their time to help advance this work. Their hope and commitment to advancing research is the key to our collective success.”

How Does TMS Work?
Transcranial magnetic stimulation (TMS) uses a magnet to activate or suppress brain activity with electricity. An electromagnetic coil is positioned against the head, over an area of the brain involved in coordinating movement. The coil delivers brief pulses of electricity through the skull, into the brain. The pulses stimulate neurons in the targeted brain region. A person receiving TMS experiences a tapping sensation on the head as the pulses are administered. The process is loud but painless. No sedation or anesthesia are needed. TMS has been approved by the US Food & Drug Administration (FDA) as a treatment for depression and obsessive compulsive disorder.

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The Dystonia Medical Research Foundation is a 501(c)(3) non-profit organization dedicated to advancing research for improved dystonia treatments and ultimately a cure, promoting awareness, and supporting the well-being of affected individuals and families.