R. Malcolm Stewart

High-Frequency Stimulation of the Subthalamic Nucleus for the Treatment of Parkinson's Disease- A Team Perspective

Parkinsons disease (PD) is a debilitating neurodegenerative disorder affecting more than 1.2 million people in the United States. Genetic and environmental toxins are believed to be risk factors in acquiring the disease. PD is characterized by tremors, rigidity, bradykinesia, poor gait, and postural instability. These cardinal symptoms improve with medication such a levo-dopa (L-dopa). However, over time, as the disease progresses, the patient becomes refractory to medication, or medication produces debilitating side effects. When this occurs or when there are worsening of symptoms, neurosurgical treatment is recommended, particularly deep brain stimulating (DBS) electrodes implanted in the subcortical subthalamic nucleus (STN). Over the last 5 years STN DBS has gained acceptance and become the neurosurgical treatment of choice for PD. To achieve maximum beneficial effects with minimum adverse effects from the surgery, the expertise of an integrated team of physicians and nurses is essential. A clear understanding of the different aspects of the procedure, including the risks and benefits of the treatment, assists neuroscience nurses in communicating with the PD patient, and providing the most appropriate, knowledge-based pre- and postoperative care.

Nonlinear temporal organization of neuronal discharge in the basal ganglia of Parkinson's disease patients.

Previous electrophysiological studies of the basal ganglia in Parkinsons disease (PD) patients have utilized linear analyses in time-or-frequency-domains to characterize neuronal discharge patterns. However, these measures do not fully describe the non-linear features of discharge rates and oscillatory activities of basal ganglia neurons. In this original research, we investigate whether non-linear temporal organizations exist in the inter-spike interval series of neurons recorded in the globus pallidus or the subthalamic nucleus in PD patients undergoing surgery for the implantation of deep brain stimulating electrodes. Our data indicate that in approximately 80% of globus pallidus and subthalamic neurons, the raw inter-spike interval sequences have lower entropy values than those observed after shuffling of the original series. This is the first report establishing non-linear temporal organization as a common feature of neuronal discharge in the basal ganglia of PD patients.

Determination of the olfactory threshold using a piezoelectric microdispenser for neurodegenerative disease diagnostics

Ink-jet microdispensing technology was used to develop an instrument for the quantitative determination of the olfactory threshold. An electrical pulse applied to the piezoelectric element produces a deformation that is transmitted to the fluid which results in a drop of fluid being ejected through the orifice mounted at one end of a piezoelectric tube. An electronic console actuates the piezoelectric dispensing elements and controls the number of drops that are dispensed and evaporated to create a fragrance cloud. The number of drops that are generated, evaporated and presented to the patients nose for detection is adjusted according to a preset algorithm until the patients threshold is discovered. Neurodegenerative disease patients tested with the developed olfactometer showed a significant elevation of their olfactory threshold as compared to normal controls. This result agrees with literature studies that indicate the sense of smell is one of the first affected by neurodegenerative disease. Through its precise control and detection capability, the digital olfactometer described in this paper can be used as an early screening tool for neurodegenerative disease through olfactory threshold determination.

Stimulation of the Subthalamic Nucleus for the Treatment of Parkinson's Disease: Postoperative Management, Programming, and Rehabilitation

High-frequency stimulation of the subthalamic nucleus is a neurosurgical procedure for the alleviation of motor symptoms of Parkinsons disease and debilitating medication-induced dyskinesias. Stimulation is achieved with electrodes implanted stereotactically in the subthalamic nucleus by a neurosurgeon specializing in stereotactic surgery and a team composed of an anesthesiologist, a neurophysiologist, certified nurses and nurse practitioners and, at some centers, a neurologist. The teamwork continues in the recovery room and the intensive care unit, where the patient may experience transient adverse behavioral effects. Two weeks after surgery, the neurostimulator is activated and programmed. The medications also are adjusted to complement stimulation to maximize the therapeutic effects and minimize the stimulation-induced side effects. For those patients who are deconditioned or have major speech, gait, or balance problems, rehabilitation therapy is employed.

Web-based evaluation of Parkinson's Disease subjects: Objective performance capacity measurements and subjective characterization profiles

Parkinsons Disease (PD) is classified as a progressively degenerative movement disorder, affecting approximately 0.2% of the population and resulting in decreased performance in a wide variety of activities of daily living. Motivated by needs associated with the conduct of multi-center clinical trials, early detection, and the optimization of routine management of individuals with PD, we have developed a three-tiered approach to evaluation of PD and other neurologic diseases/disorders. One tier is characterized as “web-based evaluation”, consisting of objective performance capacity tests and subjective questionnaires that target history and symptom evaluation. Here, we present the initial evaluation of three representative, self-administered, objective, web-based performance capacity tests (simple visual-hand response speed, rapid alternating movement quality, and upper extremity neuromotor channel capacity). Twenty-one subjects (13 with PD, 8 without neurologic disease) were evaluated. Generally good agreement was obtained with lab-based tests executed with an experienced test administrator. We conclude that objective performance capacity testing is a feasible component of a web-based evaluation for PD, providing a sufficient level of fidelity to be useful.

Investigation of a Portable Performance Measurement System for Neurologic Screening in Clinics

Motivated by the need for clinical screening for early detection of neurologic disease, a prototype portable instrument dubbed the human performance multimeter (HPMM) was developed. The HPMM is based on a set of lab-based performance capacity tests developed and evaluated over the last two decades. We attempted to integrate selected functionality of a set of modular lab-based instruments into a single, small package. In the present study, a 4th generation prototype was developed and evaluated for usability, measurement repeatability, and preliminary measurement validity. Five performance capacity tests (upper extremity coordination, isometric grip strength, simple response speed, rapid alternating movement, and steadiness/tremor) were administered to twenty healthy adult volunteers. Short-term reliability was investigated using a test-retest protocol. Most measures were found to possess good test-retest reliability (r>0.75). Preliminary validity was investigated by comparing results to those obtained with non-portable devices that served as models for the HPMM. Results were in good agreement with those instruments. It is concluded that measures of good fidelity can be obtained with this type of instrument

New methodology for identifying hierarchical relationships among performance measures: Concepts and demonstration in parkinson’s disease

Many different tests that address aspects of human performance have been reported. Yet, critical issues remain. The hierarchical organization of tests, the degree of involvement of different human subsystems, and the relationship between measures are often unclear. General Systems Performance Theory provides the basis for a novel analytic method, termed Nonlinear Causal Resource Analysis, to determine task demands (i.e., analyze tasks) and predict performance in complex tasks using only measures of lower level subsystem performance capacities. Recently, we realized new insights and discovery of a new application of these concepts to address the issues noted. A quasi-objective methodology is presented to identify hierarchical relationships among performance measures. The method is applied to seven different performance measures in a study of Parkinson’s Disease subjects (n = 3D197) exhibiting a wide range of disease severity. Resource economic interpretations of experimental data using performance theory concepts were used to define relationships between performance measures and to organize them hierarchically. This method is anticipated to have broad utility for identifying relationships between performance measures.

Restless legs syndrome: associated non-motor symptoms and medical comorbidities: a controlled study

Introduction: Restless legs syndrome (RLS) is a chronic sensorimotor disorder characterized by discomfort or pain, predominantly in the legs, resulting in an urge to move during times of rest. These disturbances are often accompanied by sleep fragmentation, which can significantly increase medical comorbidities over time and can have a detrimental effect on a patient’s overall quality of life. In this retrospective study, we examined the temporal relationship between the time of RLS diagnosis and the onset of non-motor symptoms (NMS) and medical comorbidities. Patients and methods: Thirty-six RLS patients were evaluated for age at: symptom onset, time of diagnosis, time of occurrence of NMS, and medical comorbidities. We used structured interviews, validated questionnaires, and past medical records to aggregate and verify patient data. There was no clinical evidence to suggest secondary RLS in any patient at time of diagnosis. Results: Twenty-five patients were diagnosed as having RLS alone and eleven were diagnosed with RLS and Parkinson’s disease (RLS + PD). In the RLS + PD group, irrespective of which disorder presented first, we found that patients exhibited symptoms of RLS at a significantly later age than those patients with RLS alone (P,0.05). The incidence and severity of NMS were significantly higher in the RLS + PD group compared to RLS alone and controls (P,0.001). Increased risk of RLS was identified in patients exhibiting mood changes and sleep deficits, and these risk factors manifested 5 and 10 years prior, respectively, to their diagnosis. Conclusion: Primary RLS develops earlier in those patients who only have RLS compared to those who later also develop PD. Mood and sleep impairment can be present years prior to the diagnosis of RLS. Other medical comorbidities associated with RLS included hypertension, hyperlipidemia, arthritis, chronic pain, and diabetes.