CleveMed Blogs

I remember the story of a biomedical engineer I know. As an undergrad, he planned to graduate, leave school and enter the industry. In the last weeks of class, a professor brought in a patient with a high level spinal cord injury. He demonstrated how FES (functional electrical stimulation) could be used to control weak or paralyzed muscles. When he saw this paralyzed patient move his arms, he was hooked. He went on to graduate with a PhD in biomedical engineering with a focus on rehab engineering.

Biomedical Instrumentation 101: students learn circuit design, how to build an amplifier, data acquisition, signal processing, etc. The concepts are taught; but is there enough emphasis on how this information can be used in applications outside of the classroom? Education in these areas of engineering and physiology is important, but how it can be used in real world applications is just as critical.

CleveLabs is a lab course system that uses wireless data acquisition hardware and interactive software to teach engineering, data acquisition, digital signal processing and basic and advanced physiology. In addition to these customary topics, we also include a section of clinical applications: labs that demonstrate to students where they can apply all that they’ve learned. How about using electro-oculography (movement of the eye) to control the position of a dot on the screen, and control the color of the dot just by blinking? This shows how EOG can be used for computer cursor control, where blinking represents a click, for persons with high level spinal cord injuries. Or what about using electromyography (electrical muscle activity) from the biceps and wrist extensor muscles to control the elbow angle and hand grasp of a virtual robotic arm? This explains how the use of existing muscles can control a prosthetic limb. In addition, heart rate detectors are created, gait and stride time are measured, EEG is used to detect different states of alertness. CleveLabs goes beyond the traditional topics using clinical examples of biomedical engineering applications.

Where can real world examples, such as the story of my friend, take your students?

Significant strides have been made in the management of Parkinson’s disease (PD) motor symptoms such as tremor, slowness of movement, and rigidity; however, treatment side effects pose a key therapeutic challenge. Upon initial onset of the disease, patients are typically prescribed levodopa, a drug taken orally several times a day to increase dopamine levels in the brain to alleviate motor symptoms.

As the disease progresses, changes in the body’s response to levodopa give rise to therapy complications such as delayed onset and decreased duration of motor symptom relief per dose. Chronic treatment can also lead to side effects such as dyskinesias, which can take on various debilitating forms: irregular brief rapid movements (chorea) during the “On” state at peak dose and sustained twisting movements (dystonia) during the “Off” state when the medication has worn off. Approximately 30% of patients diagnosed with PD exhibit levodopa-induced dyskinesia within 5 years of treatment^[1] and 59-100% by 10 years^[1-3]. Quality of life has been shown to be negatively impacted by dyskinesias^[4], specifically mobility^[5], activities of daily living^{[5, 6]}, communication^{[5, 6]}, and bodily discomfort^[6].

Figure 1: Blood Levodopa Concentration

Adjustments in medication to reduce drug side effects often sacrifice control of motor symptoms, and balancing this tradeoff poses a significant challenge for management of advanced PD. Alternate strategies to better control motor fluctuations have aimed efforts at developing drug administration methods to minimize swings in blood levodopa concentration. Figure 1 highlights the typical drug cycles that patients may experience throughout the day when taking levodopa in discrete intervals^[7]. Over time this approach shrinks the size of the “On” state window requiring higher doses to achieve the same effect and increasing the frequency and severity of dyskinesia. The ideal scenario would be to maintain levodopa concentration in the “On” state where levodopa is effective at alleviating motor symptoms without inducing dyskinesia. Studies have suggested that continuous drug administration may better mimic the normal physiological release of dopamine in the brain in order to attain more stable therapy benefits^{[8, 9].}

Parkinson’s disease (PD) is characterized by cardinal motor symptoms of tremor, slowness of movement, and rigidity ^[1]. Symptoms directly affect quality of life and activities of daily living by impeding coordination of multiple limbs and fine dexterity. This can be extremely debilitating, leading to decreased mobility and independence with increased risk for falling.

Current clinical PD therapies are designed to address disease motor symptoms; however, there are limitations associated with these approaches. Drug therapy (e.g., levadopa) effectiveness may decrease over time and lead to side effects such as dyskinesias (involuntary irregular movements) ^[2]. Patients may eventually consider surgical procedures such as deep brain stimulation when increased drug dose side effects outweigh the benefits. This procedure, however, has limitations and risks, such as improper lead placement, decreased effectiveness over time, and not being appropriate for all patients ^[3].

While treatments such as drug therapy and surgical procedures are clinical standards, new research suggests exercise as a potentially less invasive alternative/adjunct treatment. It has been well established that exercise reduces risks of developing chronic diseases such as cancer, obesity, and heart disease ^[4-6]. Such benefits of exercise can also be translated to motor improvement in PD ^{[7, 8].} The general concept behind the benefit of exercise in PD suggests that physical exercise may stimulate specific biochemical changes to induce production of dopamine, a neurotransmitter involved in allowing the body to perform smooth controlled movements ^[9]. The sedentary lifestyle associated with PD promotes further motor symptom impairment through muscle weakness, postural imbalance, and increased risk of falling ^[10]. Thus, there exists an urgency to develop PD-specific exercise regimens early in disease progression in an attempt to break or delay this debilitating cycle.

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.