New technology explores the prediction of the freezing of gait to improve lives.

In January 2018, Helen Bronte-Stewart’s neurology lab at Stanford published a paper in Movement Disorders detailing an experiment that monitored the effectiveness of coordinated reset vibrotactile stimulation, electrical impulses meant to “reset” neuron bodies, for Parkinson’s patients as shown in the image below. More specifically, the researchers sought to alleviate a Parkinsonian symptom known as freezing of gait where a patient suddenly feels as if “their feet are ‘stuck to the floor as if held by magnets,’” leaving them thus unable to move (Weiss, 2020).

Gait Monitoring of Coordinated Reset Vibrotactile Stimulation for Parkinsonian
(Image: M. DePoint, University of Minnesota)

Parkinson’s Disease is a neurodegenerative disorder thought to be caused by the loss of dopamine-producing cells in a region of the brain in the upper brainstem known as the substantia nigra (Parkinson’s Disease Information Page). Since dopamine is a neurotransmitter vital to movement regulation, some of the most common Parkinsonian symptoms include tremors (shaking that occurs generally at rest), bradykinesia (slowness of movement), muscular rigidity (stiffness and inflexibility), and postural instability (impaired balance) as shown in the image below.

While there is currently no cure for this disease, drugs like levodopa, which is turned into dopamine by the body, can make an impactful difference in the patient’s quality of life by helping them control their symptoms. However, levodopa does not resolve all of the patient’s symptoms like freezing of gait (FOG) a symptom which 53% of patients with moderate to advanced Parkinson’s experience. Scientists have shown that FOG is an expression of the high asymmetry and arrhythmicity in the patient’s gait cycle. Asymmetry refers to the patient being unable to swing their arms with one another as one arm swings more than the other while arrhythmicity refers to the patient being unable to maintain a consistent stride time. As freezers have higher gait asymmetry and arrhythmicity than non-freezers, correcting the asymmetry and arrhythmicity could potentially stop future freezing episodes. This is where the Bronte-Stewart lab comes in.

Parkinson’s Disease Infographic
(Image: Froedtert, Froedtert and Medical College of Wisconsin)

The basis of their work is the use of peripheral vibrotactile coordinate reset stimulation (PVCRS), which works by using electrical stimulation through the peripheral nervous system to reset populations of neurons, ending any aberrant neuronal synchrony. Using a turning and barrier course which elicits freezing episodes a third of the time, these researchers tested how five Parkinson’s patients would respond. In order to measure the results of this experiment, they used “a blinded rating of the Unified Parkinson’s Disease Rating Scale (motor, UPDRS III), quantitative measures of forward walking using 9-axis inertial measurement units (APDM Inc.), and the kinematics of repetitive wrist flexion-extension (rWFE) using solid-state gyroscopes (Motus Bioengineering)” according to Syrkin-Nikolau et al. (2018). The Unified Parkinson’s Disease Rating Scale was used to determine the severity of the patient’s Parkinson’s by having a neurologist assign a rating from zero to four based on the patient’s motor movements (Team, Diagnosis – Rating Scales 2017). The inertial measurement units were attached like a Fitbit might be and measured the patient’s gait and balance so that researchers could reliably determine episodes of freezing. The solid-state gyroscopes were attached to the patient’s hand and used to measure the angular velocity of the wrist flexion-extension in order to measure wrist bradykinesia. After doing some experimenting, the Bronte-Stewart lab determined that three days of peripheral vibrotactile coordinate reset stimulation was tolerable and resulted in an increase of repetitive wrist flexion-extension, which corresponds to reduced bradykinesia, along with an acute reduction of arrhythmicity and asymmetry as shown in the image below. In the long term, there was also a general reduction of asymmetry and an increase in repetitive wrist flexion-extension. The experiment, in short, was a definite step forward towards using PVCRS for Parkinson’s treatment.

Data of Acute Effects of PVCRS (A-C) and of Long-Term Effects of PVCRS (D-F)
(Image: Syrkin-Nikolau, et al., Wiley Movement Disorders)

The future of this technology is largely based on predicting the freezing of gait before it even happens to help Parkinson’s patients avoid FOG altogether. Implanted units like the Activa PC+S from Medtronic, a type of deep brain stimulation, was what Johanna O’Day, one of the authors on the paper, suggested may be used. These units relay kinematic and neural data to the patient’s neurologist, hence their nickname “brain radio,” and deliver electrical stimulation in real time. The goal is that these units can one day adjust the voltage and frequency of the electrical stimulation at any time based on the patient’s specific movements. This, in turn, will drastically reduce Parkinsonian symptoms like FOG among other symptoms potentially. In this way, the Bronte-Stewart lab’s work seeks to improve the lives of millions of patients around the world living with Parkinson’s.

References

Weiss, H. (2020, March 23). Dr. Howard Weiss Discusses “Freezing of Gait” in Parkinson Disease. Retrieved October 03, 2020, from http://parkinsonfoundation.org/blog/dr-howard-weiss-discusses-freezing-gait-parkinson-disease DePoint, M. (2014, April 2). U of M researchers monitor gait initiation via high-speed cameras and electronic sensors. Retrieved from https://www.healthtalk.umn.edu/2014/04/02/u-m-researchers-study-freezing-gait-people-parkinsons-dise ase/ Parkinson’s Disease Information Page. (n.d.). Retrieved October 03, 2020, from https://www.ninds.nih.gov/Disorders/All-Disorders/Parkinsons-Disease-Information-Page Parkinson’s & Movement Disorders. (2020, July 15). Retrieved October 03, 2020, from https://www.froedtert.com/parkinsons-movement-disorders Team, E. (2017, March 8). Diagnosis – Rating Scales. Retrieved October 03, 2020, from https://parkinsonsdisease.net/diagnosis/rating-scales-staging/ Syrkin-Nikolau, J., Neuville, R., O’day, J., Anidi, C., Koop, M. M., Martin, T., . . . Bronte-Stewart, H. (2017). Coordinated reset vibrotactile stimulation shows prolonged improvement in Parkinson’s disease. Movement Disorders, 33(1), 179-180. doi:10.1002/mds.27223 Syrkin‐Nikolau, J. (2018). Coordinated reset vibrotactile stimulation shows prolonged improvement in Parkinson’s disease. Wiley Movement Disorders. doi:10.1002/mds.27223