Posts Tagged ‘dyskinesia’

Optimizing Drug-Induced Side Effects in Parkinson’s Disease

Friday, January 15th, 2010

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

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].

1. Van Gerpen, J.A., et al., Levodopa-associated dyskinesia risk among Parkinson disease patients in Olmsted County, Minnesota, 1976-1990. Arch Neurol, 2006. 63(2): p. 205-9.
2. Colosimo, C., et al., Motor fluctuations in Parkinson’s disease: pathophysiology and treatment. Eur J Neurol, 1999. 6(1): p. 1-21.
3. Grandas, F., et al., Risk factors for levodopa-induced dyskinesias in Parkinson’s disease. J Neurol, 1999. 246(12): p. 1127-33.
4. Pechevis, M., et al., Effects of dyskinesias in Parkinson’s disease on quality of life and health-related costs: a prospective European study. Eur J Neurol, 2005. 12(12): p. 956-63.
5. Chapuis, S., et al., Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord, 2005. 20(2): p. 224-30.
6. Damiano, A.M., et al., Evaluation of a measurement strategy for Parkinson’s disease: assessing patient health-related quality of life. Qual Life Res, 2000. 9(1): p. 87-100.
7. Keijsers, N.L., et al., Online monitoring of dyskinesia in patients with Parkinson’s disease. IEEE Eng Med Biol Mag, 2003. 22(3): p. 96-103.
8. Olanow, C.W., et al., Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications. Lancet Neurol, 2006. 5(8): p. 677-87.
9. Olanow, C.W., Levodopa/dopamine replacement strategies in Parkinson’s disease–future directions. Mov Disord, 2008. 23 Suppl 3: p. S613-22.

Kinesia with automated tremor scoring released: the first device of its kind

Wednesday, January 28th, 2009

Kinesia is a system for objectively monitoring and tracking the severity of Parkinson’s disease symptoms in conjunction with clinician evaluations using the Unified Parkinson’s Disease Rating Scale (UPDRS). The device uses tiny motion sensors (accelerometers and gyroscopes) to collect patient symptom data and, using a Bluetooth radio, wirelessly transmits that information to a PC. An addition to the system has just been released which includes automated tremor scoring based on the 0-4 scoring method of the UPDRS. Before Kinesia, there was no objective way to consistently track symptoms, making this a large advance in the way Parkinson’s disease patients are monitored.

The Kinesia patient unit is worn on the hand and wrist while patients follow video instruction for completing upper extremity motor tasks. After the completion of the tasks, algorithms in the software automatically score three tremor tasks for evaluating rest, postural and kinetic tremor on a 0-4 scale based on the UPDRS. In addition to the scoring being automated and repeatable, the scores are provided with better resolution than the whole numbers given with the UPDRS. Kinesia will assign scores such as 1.29, 3.75 or 0.84 to provide clinicians with a more exact picture of a patient’s symptoms. Reports can be generated and tremor symptom history can be viewed by their clinician, assisting them in making decisions regarding the progression of the disease, the patient’s current medication or other methods of treatment. A peer reviewed publication documenting clinical utility was accepted by The Movement Disorders Journal and is currently available online at http://www3.interscience.wiley.com/journal/121634261/abstract

There are many other symptoms that affect PD patients outside of tremor, including bradykinesia (slowed movements or hesitations), rigidity, gait and balance issues and dyskinesias (wild, involuntary movements caused by an overabundance of dopamine in the brain – the result of a patient being overmedicated). Automated tremor scoring is only the beginning of the development of Kinesia . Researchers at CleveMed are in the process of conducting a large clinical trial involving three movement disorders centers and one hundred fifty PD patients. The data collected during this study will aid in the development of algorithms for automated scoring of bradykinesia and dyskinesias. The overall goal is to include scoring for a large majority of the motor symptoms that affect PD patients.

Current Parkinson’s Disease Motor Symptom Assessment Methods May Leave Room for Improvement

Wednesday, January 21st, 2009

Kinesia is a compact patient worn device that was developed to measure and assess the severity of the motor symptoms associated with Parkinson’s, including tremor and bradykinesia. For more information on Parkinson’s, click here. Currently, symptoms are assessed using a subjective rating system called the Unified Parkinson’s Disease Rating Scale, or UPDRS. During a typical exam, patients are instructed to perform a series of motor tasks for evaluating symptoms. While the tasks are completed, a clinician watches and visually assess the symptoms, assigning a 0-4 score based on the severity with 0 being the absence of symptoms and 4 being the most severe.

Because of the subjective nature of the UPDRS, there is definitely room for error. Studies have shown that clinicians can score the same symptom severity differently on different days and different clinician scores can vary for the same severity level. Also, patient’s symptoms can vary greatly throughout the course of a day and a one time clinical visit can not capture these fluctuations. It is important to have a method that objectively and consistently tracks patient’s symptoms at the clinic and at home.

Better tracking of symptoms can be incredibly helpful for Parkinson’s patients. Medication is usually the first method of treating symptoms and there is a fine line between under-medicating a patient which can cause symptoms to still persist, prescribing just the right amount and over-medicating a patient which causes a patient to become dyskinetic, or to have wild involuntary movements.

Kinesia is a device that is worn on the hand of the patient while they complete tasks for assessing tremor and bradykinesia. The device then, using algorithms built into the software, automatically assigns a 0-4 score for the tasks. Kinesia provides a consistent repeatable method for evaluating and scoring symptoms and more objectively track the progression of the disease. The device can also be sent home with a patient and the tasks completed at regular intervals to monitor the fluctuation of the patient’s symptoms. Tracking these fluctuations with Kinesia could assist a clinician in regulating medication time and dosage, leading to increased time without symptoms and less of a risk of under or over medicating.

The latest version of Kinesia was just released in January, so check back regularly for updates on the device being used in the field, current clinical trials and new uses for Kinesia. Ultimately, the hope is to assist in creating an improved quality of life for Parkinson’s patients in the US and around the world.