CleveMed Blogs

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.

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.

While tremor is often the most visible symptom of Parkinson’s disease, bradykinesia can be the most impairing to the patient. The term "bradykinesia" literally means "slowed movements"; however, in the literature, the "bradykinesia" is often used synonymously with the terms "akinesia" and "hypokinesia." Technically, "bradykinesia" only refers to slowness of movement; however, lack of spontaneous movement (akinesia) and smaller than desired movements (hypokinesia) are often grouped together as "bradykinesia." This misuse in terminology can result in widespread variability in clinical ratings.

The standard clinical method for evaluating bradykinesia is qualitative assessment by a clinician and score assignment (0 – 4) based on the Unified Parkinson’s Disease Rating Scale (UPDRS). This score is assigned while the subject completes repetitive tasks of finger-tapping, hand opening-closing, and pronation-supination. Evaluators are instructed to account for a wide array of factors such as speed, amplitude, fatiguing, hesitations, arrests in movement, and how these variables change during the task. This is challenging to even the most experienced movement disorder specialist. A given patient could be scored a 2 on the UPDRS finger-tapping task due to slow and large amplitude movements or fast and small amplitude movements. It is difficult to gauge weights that specific clinicians place on different bradykinesia manifestations.

The inconsistency among raters may have implications beyond symptom severity assessments. Recent data have shown that speed and amplitude respond differentially to dopaminergic medication ^[1]. Furthermore, it is unknown if the underlying neural mechanisms that cause the various bradykinesia manifestations are the same. A quantitative understanding of different bradykinesia features could ultimately lead to the development of more targeted treatments for specific patients with Parkinson’s disease.