CleveMed Blogs

Hello! My name is Danielle Madere, a recent graduate from Illinois Institute of Technology with a bachelor’s degree in biomedical engineering. In the past month, I was lucky to join the CleveMed family as their newest biomedical engineer.

My first two weeks on the job consisted of gaining familiarity with some of our devices: Kinesia, KinetiSense, and the BioRadio. There was also much training, many meetings, and assisting with grant writing.

In the coming months, I will be focusing a lot of my time on clinical studies for several movement disorder monitoring products that we are currently focusing on, specifically ETSense, ParkinStep, and PDRemote. I will be organizing meetings with patients, collecting symptom data, and performing some preliminary analysis to ensure the data we are collecting is valid.

I am very excited to work with CleveMed’s Movement team because I truly believe that our devices, such as Kinesia HomeView, will revolutionize the way clinicians treat movement disorders such as Parkinson’s disease. Presently, Parkinson’s disease symptoms are rated by the clinician, based solely on the clinician’s subjective opinion of the severity (UPDRS). Additionally, clinicians only see the patient for a very limited window of time in their office, which does not provide significant insight into the symptoms a patient faces at home, where treatment really matters. Kinesia HomeView will allow clinicians to observe the quality of life of a patient throughout the course of a day in the comfort of their own home, and adjust medication doses and frequency accordingly.

The more closely I interact with Parkinson’s disease and essential tremor patients, the more desperately I want to help improve their quality of life, and CleveMed gives me that opportunity, which I am eternally grateful for.

The Movement Disorders Division of CleveMed has primarily focused on monitoring motor symptoms associated with Parkinson’s disease (PD). A more common movement disorder is essential tremor (ET), which affects approximately 4% of the population over age 40 in the United States. In Parkinson’s disease, tremor (involuntary shaking) occurs primarily at rest, but essential tremor is mainly characterized by tremor of a moving limb.

Measuring Tremor

Subjective Rating: Tremor associated with essential tremor is traditionally rated by various subjective tremor rating scales. These scales all provide a discrete, subjective symptom rating at a discrete point in time. They require a clinician to visually assess the patient, and cannot capture complex fluctuations that occur throughout the day in response to interventions.

Objective Rating: Objectively capturing essential tremor symptoms continuously during daily activities, and using adaptive algorithms to both classify tremor types and severity, could help clinicians better adjust therapy to minimize symptom fluctuations, and expand care to rural and underserved populations. Therefore, CleveMed has recently begun development on a system to objectively monitor essential tremor.

CleveMed previously developed a compact wireless system, Kinesia™, to quantify Parkinson’s disease symptoms. In a clinical study, this system successfully demonstrated objective quantification of Parkinson’s disease motor symptoms. These promising results for Parkinson’s disease suggest the system may be adapted for quantifying tremor in essential tremor patients by developing specific ET algorithms. More continuous portable monitoring can capture the tremor fluctuations that can occur throughout the day. Using a combination of accelerometers and gyroscopes will provide a system with much greater sensitivity for tremor type discrimination and severity rating. (Existing systems contain only a single-axis accelerometer). Continuous ratings throughout the day can aid clinicians and researchers in therapy development and optimizing symptom management for patients with essential tremor.

One of the most difficult aspects of monitoring Parkinson’s disease (PD) motor symptoms, is that the severity of tremor and bradykinesia (slowed movements) greatly fluctuates throughout the day.

When medication is at its peak effectiveness, the patient is said to be “On.” Similarly, when medication has completely worn off, the subject is said to be “Off.” Symptoms are often worst first thing in morning, but improve after the first dose of medication. However, as the medication wears off, symptoms return mid-day. These cycles of waxing and waning motor symptoms continue throughout the day. Controlling these “On” and “Off” cycles can be difficult, as patients with PD are typically evaluated in the neurologists’ office, which only allows the physician to capture a snapshot of motor symptoms. Furthermore, patients typically are instructed to refrain from taking medication the night prior to the office visit. A state of anxiety in this condition may amplify PD symptoms during motor evaluation. Monitoring motor symptoms at home would provide clinicians with improved tracking of these complex motor fluctuations and in-turn optimize medication dose to improve patient quality of life.

Kinesia is a compact wireless system developed by CleveMed to quantify movement disorder symptoms. In clinical trials, Kinesia objectively quantified tremor and bradykinesia in PD patients in the clinic. Objective symptom ratings output by the Kinesia system were highly correlated to clinician ratings. CleveMed has recently begun a clinical study in which the Kinesia system is being used throughout the day, at home, by patients with PD. Preliminary results demonstrate that Kinesia can capture the “On” and “Off” motor symptom fluctuations in a subject’s home. Monitoring PD symptoms on a more continuous basis at a patient’s home should improve clinical outcomes and decrease costs especially for disparate patient populations in areas not in close proximity to movement disorder specialists.

Parkinson’s disease is a neurodegenerative disease of the central nervous system and is primarily characterized by cardinal motor symptoms such as tremor, bradykinesia (slowness of movement), and rigidity. Lower extremity symptoms such as gait and balance disturbances (initiating movement, freezing of movement, improper movement form), especially in advanced patients, can be very debilitating, leading to decreased mobility and independence, decreased quality of life, and an increased falling/hip fracture risk ^[1]. A positive PD diagnosis occurs when a minimum of two cardinal symptoms present themselves. However, less attention is given to gait and balance abnormality as it typically develops in the advanced stages of PD.

Standard clinical assessment of gait and balance based on a 0 (no severity) – 4 (high severity) scale is performed using a subset of the Unified Parkinson’s Disease Rating Scale (UPDRS) motor section. Tasks typically consist of foot stomping while seated, gait assessment while walking, arising from chair with arms crossed over the chest, and balance assessment while being pulled backwards. As gait is particularly sensitive to ON-OFF therapy state changes in PD and incorporates upper extremity function such as arm swing as well as rigidity and bradykinesia in lower extremities, gait analysis may be a reliable method of assessing overall motor function over time in PD ^[2].

When diagnosed with PD, the first line of treatment typically consists of L-Dopa medication to alleviate motor symptoms. However over time, drug effectiveness decreases, requiring the patient to increase dosage. Frequent and stronger side effects such as dyskinesias (uncontrolled arm movement) and unpredictable “on”/”off” episodes are cause for more invasive therapeutic intervention. Deep brain stimulation (DBS) has been widely recognized as an appropriate treatment option when medication no longer adequately alleviates motor symptom severity. Several therapy targets have been established for PD. Subthalamic nucleus (STN) and Globus Pallidus Interna (GPi) stimulation are recognized treatments for sustained improvement in tremor, rigidity, and bradykinesia ^{[3, 4]}. However the effects on gait disturbance are less understood. During DBS lead placement and post-evaluation, neurologists adjust several settings: electrode contact configuration and stimulation parameters (frequency, pulse width, and amplitude). Studies show that while high-frequency/high voltage stimulation improves cardinal symptoms, patients exhibit increased frequency of freezing episodes. However, stimulation at lower frequencies has demonstrated improved gait ^[5].

New PD gait therapies are being researched and developed and existing interventions further established. Another DBS target, the pedunculopontine nucleus (PPN), located near the brain stem plays an important role in locomotion function in animal models, specifically initiation and modulation of gait ^[6-8]. Patients with advanced stages of PD only exhibit mild improvement of freezing with standard medication such as L-Dopa ^{[9, 10]}. Preliminary studies of PPN surgeries off-medication marked a significant improvement of the UPDRS motor exam section III, specifically gait and postural qualities. In addition, the combination of STN and PPN DBS resulted in a further significant improvement. Despite promising results, PPN surgical intervention is currently in its infancy as little is known about the nucleus’ function in humans and how well animal model testing translates to human clinical trials ^[7].