Zapping the brain to help ataxia

Written by Dr. Judit M. Perez Ortiz Edited by Dr. Sriram Jayabal

In a new study, scientists have found that “zapping” the brain with an electromagnetic wand may someday help patients with spinocerebellar ataxia.

In an era of ever-evolving technological advances used for personal entertainment and space travel, medical scientists are harnessing the power of electromagnetism to safely penetrate the skull and manipulate brain cells by mimicking their favorite language – electric current.

Clinicians currently have access to powerful and effective tools designed to stimulate brain cells (known as neurons) for various neurological and psychiatric conditions. Spinocerebellar ataxias (SCAs), however, are not yet in the mix. Though several techniques exist, the methods used to stimulate neurons in the brain can be broadly classified into invasive and non-invasive approaches. For instance, Vagus Nerve Stimulation is used for drug-resistant epileptic seizures, while Deep Brain Stimulation is used for Parkinson’s disease and severe depression. In both instances, a surgical procedure is required because the implanted electrodes have to come in direct contact with the target nerve or brain structure. Disadvantages associated with these surgical methods include the risk of infection, bleeding, and hardware malfunction. Non-invasive approaches to stimulate the brain include electroconvulsive (“shock”) therapy, in which electrodes are placed on the scalp surface to provoke a controlled seizure that yields a therapeutic effect. However, shock therapy requires anesthesia, and patients run the risk of memory issues as a side effect. A second non-invasive brain stimulation tool is also available, called repetitive Transcranial Magnetic Stimulation (rTMS). There are many factors that make rTMS clinically appealing: it does not require surgery, it is already FDA-approved (for severe depression), it is painless, and it has been found to be safe. Further, unlike the broad brain stimulation achieved by electroshock therapy, rTMS delivers a more precise stimulation in a defined brain region, which leaves untargeted brain regions untouched.

cartoon of neuronal brain cells and electricity flowing between them
Artist’s depiction of electrical signals in the brain. Image courtesy of flickr.

Besides its circular or figure-eight attachment, the rTMS device looks quite a bit like a magic wand. Though this is no wizard’s tool, you could say that it does cast a powerful spell: the attachments on the end of the rTMS device are electromagnetic coils, which have the power to “zap” specific brain regions. In a remarkably simple procedure, the wand is gently placed over the patient’s scalp, where it delivers electromagnetic pulses that create just enough electric current to stimulate underlying brain cells without adversely affecting them.

A new pilot study conducted at the Beth Israel Deaconess Medical Center found that using rTMS to stimulate the cerebellum of SCA patients is safe and may improve some aspects of ataxia. First, the investigators recorded the study participants’ baseline movement performance using a battery of tests designed to evaluate different features of ataxia, including balance, gait, and posture. Then, half of the study participants were randomly assigned to receive rTMS, while the other half were assigned to the control, or “sham” group.

In both groups, the participants were “blinded,” meaning that they underwent the exact same procedure so they wouldn’t know if they were getting the treatment or not. The participants were told to sit in a chair and lay their heads on a pillow placed on a table. The magnetic coil was then placed over their scalp and used to deliver a specific strength and number of magnetic pulses. The pulses were delivered over three adjacent regions in the back of the skull over the cerebellum (one of the primary brain areas affected in SCA). These brief sessions were done five times per week over the course of four weeks. The only difference in the sham/control group is that the electromagnetic coil was not turned on, and so it could not stimulate the brain.

One important aspect of the protocol was the consistent and accurate repeated stimulation of the same brain region during the study period. The investigators made a brain map of each study subject by taking a detailed 3D “picture” of the brains using magnetic resonance imaging (MRI). Then, a neuronavigation system helped guide the rTMS coil placement to stimulate the target brain regions. This neuronavigation system made sure that the cerebellar structures stimulated by the rTMS were the exact same each day, and with each subsequent session. More importantly, it also ensured that the same cerebellar regions were stimulated between patients. This helps to avoid wondering if a stimulation didn’t work simply because it did not stimulate the correct neurons or because there was, in fact, no effect.

After treatment with rTMS, the study subjects were again evaluated to determine if any of their ataxia symptoms had improved. The investigators found that after just twenty sessions, the subjects receiving rTMS demonstrated an improvement in the ability to balance while standing. Balance is important for everyday tasks and to keep us from falling or getting injured. This finding was consistent in two tests – a subjective clinical evaluation by a doctor (“stance” in the SARA ataxia scale) and an objective, quantifiable measure (postural sway fluctuations). This is exciting because it shows that noninvasively stimulating the cerebellum could produce a measurable improvement that lasts up to 1 month. However, the study also found that there was no significant improvement in ataxia involving manual dexterity, walking, or speech after rTMS. This is important to know because it can help guide investigators to test other parameters or target brain regions with rTMS in order to alleviate other symptoms of ataxia.

While it is a pilot clinical trial, this work has several strengths in the study design that help make the findings more compelling.  As mentioned above, the study participants were randomly assigned to two groups: one receiving treatment and a control group that did not receive treatment (making this a controlled clinical trial). Having a control group allows the scientists to ascertain whether an intervention truly helped or if improvements were seen by chance. The study was also double-blinded (neither the study participants nor the clinicians evaluating them knew the identity of the treatment for each person). This is one way to avoid false improvement of symptoms, known as the placebo effect. Finally, the intervention was guided by neuronavigation, which helped standardize the treatment delivery to targeted brain regions.

However, pilot studies are not generalizable to the entire population of target patients. Pilot studies rely on a small group of human participants to get a glimpse into the possible effects of one intervention. In this study, the random distribution of subjects to treatment or sham groups resulted in there being uneven representation of the SCA types. Specifically, 8 of the 10 subjects in treatment arm had SCA3 (the other two had SCA6), while the sham group was much more diverse: SCA1, SCA2, SCA3, SCA8, and SCA14 were represented among the control participants. This is important because spinocerebellar ataxias are diverse, with distinct genetic identities and clinical features.

So, what does this mean for SCA patients? Because this is a pilot study with a small group of participants, large scale clinical trials will need to be done to validate these findings and clarify what patient groups rTMS could help and to what extent. Further, several questions remain unanswered. How long does the improvement last, for instance? How many sessions are needed to sustain an improvement? What other symptoms could cerebellar rTMS improve that were not evaluated here? Could different rTMS parameters help improve any of the other ataxia symptoms? Of course, these types of questions will need to be worked out as the investigators continue to explore the possibilities and limitations of this exciting method of treatment. It is also worth noting that finding these answers won’t be possible without patient participation in clinical trials, which will certainly be needed to move these novel therapies forward in the future.

In the big picture, SCAs are very rare, and each type of SCA is rarer still. Nevertheless, SCAs are not trivial. Symptoms can show up at any point in life and have a meaningful impact in the lives of those affected. SCA affects a person’s ability to balance, walk, eat, talk, and/or dress, and can shorten life expectancy. Moreover, SCAs are hereditary, which means they impact entire families. This affects not only caregiver roles, but also family planning decisions.

While SCAs are genetically diverse, they have cerebellar dysfunction in common. Developing therapies that target cerebellar motor symptoms could, therefore, help patients with multiple different forms of SCA. This would represent an incredibly appealing therapeutic opportunity. If proven effective in larger studies, cerebellar rTMS could become an alternative or complementary form of treatment to help improve symptoms and quality of life for SCA patients.

Key Terms

rTMS: repetitive Transcranial Magnetic Stimulation. It uses a magnet to stimulate certain parts of the brain for therapeutic purposes.

SARA score: a scoring system used by clinicians to evaluate the severity of motor deficits associated with ataxia. For more information see our Snapshot on the SARA score.

Postural sway: the horizontal displacement of a person’s body around their center of gravity. It is a measure of balance, which integrates information from different systems that collectively tell us where we perceive our bodies to be in space. More postural sway means less balance, and vice versa.

Neuronavigation system: a computer-based brain mapping system. It uses brain imaging data and mathematical modeling to recreate a 3D-model of the brain in a computer. Doctors use this coordinate system to identify brain structures inside the skull with accuracy.

Conflict of Interest Statement

The authors and editor declare no conflict of interest.

Citation of Article Reviewed

Manor B, Greenstein PE, Davila-Perez P, Wakefield S, Zhou J, Pascual-Leone A. Repetitive Transcranial Magnetic Stimulation in Spinocerebellar Ataxia: A Pilot Randomized Controlled Trial. Front Neurol, 2019;10:73. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380199/)