Parkinson’s disease
Brief about the body movement: the dopamine function
The idea of controlling body movement is mainly based on signals between three
significant parts of the brain: the cerebral cortex, thalamus, and basal ganglia. The
basal ganglia, located in the cerebrum, contains the dorsal striatum. The dorsal
striatum is the most crucial in the cognitive control of motor functions. It consists
of the caudate nucleus and the putamen “stratum”. To initiate a body movement,
the cortex sends signals to the dorsal striatum, moving to the thalamus by the
Globus Pallidus Internus. Then, the thalamus sends back the signals to the cerebral
cortex. The control of this movement is based on the dopamine release that sends
excitatory (dopamine one receptor) or inhibitory neurotransmitters (dopamine two
receptor) in substantia nigra [1].
Parkinson’s disease mechanism
The patient with Parkinson’s disease suffers from a reduced amount of dopamine
in the substantia nigra (a part of the brain that is responsible for dopamine) due to
the death of the dopamine cells. The cells die due
to several causes such as protein misfolding,
defective proteolysis, mitochondrial dysfunction,
etc. Accordingly, it prevents the second
dopamine receptor from sending inhibitory
receptors, causing the Globus Pallidus Internus
and externus (parts of the brain responsible for
inhibitory functions) to be very active. Thus, the
thalamus (a part that is responsible for relaying
motor and sensory signals) is excessively
inhibited, causing suppression of the
thalamocortical spinal pathway and forcing the
signals from the basal ganglia not to be returned
back to the cerebral cortex again.
Figure 1: this figure illustrates the sequence
of the signals’ delivery between the thalamus,
cerebral cortex, and basal ganglia parts [2].
1
Parkinson’s motor symptoms
Parkinson’s disease causes many motor and non-motor symptoms; however,
mainly motor symptoms are being aided using Assistive technology devices. One
of the most common symptoms is tremor, mainly caused in hands, legs, eyes, and
lips. Another common symptom is slowed movement (bradykinesia), where the
patient impairs mobility over time, making routine tasks become complex and
time- consuming. Lastly is rigidity; it is defined as arm or leg stiffness beyond
what would result from normal aging or arthritis. The rigidity can occur on one or
both sides of the body, resulting in a reduced range of motion.
Vibrating therapy solution
Multiple Assistive Technology devices or systems
have been made to make patients with these motor
symptoms more independent and more capable.
One of these systems is High frequency
transcutaneous electrical nerve stimulation
(TENS), or industrially named as vibrating therapy
devices.
Mechanism and Advantages
High frequency transcutaneous electrical nerve
stimulation (TENS) has been widely studied and
used in the treatment of nociceptive and
neuropathic pain [3]. Most studies suggest that
treatment with TENS in patients who have tremors
improved their muscle strength and reduced
tremors.
Figure 2: Cala Trio transcutaneous
electrical nerve stimulation. The median and
radial nerves, which project to the ventral
intermediate nucleus of the thalamus, are
stimulated by Cala Trio (Cala Health,
Burlingame, CA, USA) through two working
electrodes placed [3].
In 2018, Cala ONE was the first wearable
transcutaneous electrical nerve stimulator to be approved by the FDA [4]. Cala
ONE was improved throughout the years, making their last version Cala TRIO.
Cala Trio utilizes a specific electrode configuration placed on the wrist to target the
median and radial nerves. These electrodes are positioned on the anterior and
posterior surfaces of the wrist, respectively. The device contains an accelerometer
to measure the patient's tremor frequency, which allows for personalized
calibration of the stimulation intensity.
2
By delivering electrical signals to the median and radial nerves in the upper limbs,
Cala Trio aims to stimulate the peripheral sensory nerves connected to the ventral
intermediate nucleus (VIM) and neural circuits involved in essential tremor (ET).
This approach resembles deep brain stimulation (DBS) as it causes rapid
oscillations in the thalamus, disrupting the pathological tremor oscillations.
A study involving patients with tremors from Parkinson's disease demonstrated a
tremor suppression rate of 57% when electrically stimulating the median and radial
nerves. Over time, the stimulation provided by Cala Trio normalized the neural
activity, resulting in reduced tremor severity.
Disadvantages
Cala Trio had an open-label, single-arm design, which limits the generalizability of
its effects. To assess the therapy's efficacy more comprehensively, future studies
with more robust designs, such as randomized controlled trials (RCTs), would be
valuable.
Additionally, there are specific contraindications for using Cala Trio. It should not
be used by individuals with implanted electrical medical devices, suspected or
diagnosed epilepsy or other seizure disorders, or during pregnancy. Moreover, it
should not be applied to skin eruptions, open wounds, cancerous lesions, or
swollen/infected/inflamed areas. These contraindications highlight the importance
of careful consideration and consultation with healthcare professionals before
using Cala Trio.
References
1- J. L. Lanciego, N. Luquin, and J. A. Obeso, “Functional neuroanatomy of the
basal ganglia,” Cold Spring Harb. Perspect. Med., vol. 2, no. 12, p. a009621,
Dec. 2012, doi: 10.1101/cshperspect. a009621.
2- J. E. Hall and J. E. Hall, Pocket companion to Guyton and Hall Textbook of
Medical Physiology. St. Louis: Saunders, 2011.,
3- Mo, J., & Priefer, R. (2021). Medical Devices for Tremor Suppression: Current
Status and Future Directions. Biosensors, 11(4), 99.
4- Food and Drug Administration, HHS (2018). Medical Devices; Neurological
Devices; Classification of the External Upper Limb Tremor Stimulator. Final
order. Federal register, 83(201), 52315–52316.
3