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A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used and proven to be highly effective in helping alleviate symptoms of Parkinson’s disease (PD). Nevertheless, although high‐frequency DBS (>120 Hz) is initially effective in improving patients’ motor symptoms (mainly bradykinesia and tremors), many patients still develop gait disturbances, such as freezing of gait (FOG). Recent studies have reported that stimulation of the STN with low frequencies produce positive effects on gait disorders and reduces the number of FOG events. As research is being done to investigate how reduced DBS frequencies will affect gait and balance control, it is also important to understand what effects reduced DBS stimulation will have on their PD symptoms. The aim of this study was to investigate the effects that reduced DBS frequencies have on the severity of PD patients’ symptoms. The effects were studied in twelve PD patients (receiving DBS treatment) after reducing their DBS frequency. The varied DBS frequencies included: their clinically determined stimulation setting (CDS), a low stimulation setting (30 Hz), and an intermediate stimulation frequency (80 Hz). Symptom severity was measured using the Unified Parkinson’s Disease Rating Scale (UPDRS‐III), and the Hoehn‐Yahr (HY) stage score. The results were supportive of what we expected; that as DBS frequencies are decreased from the patients’ clinically determined setting, the clinical symptoms worsened. This is an important observation which will allow the appropriate clinical decisions be made as we continue to investigate the effects of reduced frequency DBS on gait and posture control.

Electrical eddy currents can be induced inside biological tissue by time-varying magnetic fields according to Faraday's law of induction. These eddy currents are responsible for biological effects such as visual sensations in eyes called magnetophosphenes and they accelerate the healing process of fractured bones in magnetotherapy operation. Induced eddy currents also cause neuromuscular stimulation of cardiac muscle, shown as a disturbance in the electrocardiogram and respiratory disturbance shown as a brief period of apnoea (stopped breathing) and muscle contraction in the forearm and finger. Brain cortex also can be stimulated by pulsed magnetic fields. A transient decrease in blood flow in the human skin is seen as a result of exposing the skin to pulsed magnetic fields. To study the effects of time-varying magnetic field, a method is needed to assess and measure induced current densities. Many attempts have been made to find such a method, both theoretically and practically. A theoretical model with homogenous and isotropic concentric loops of tissue was suggested but biological tissues are neither homogenous nor isotropic. A Hall effect method using a slab of semiconductor was suggested for measurement of current densities inside tissues, but this method ignored disturbances in the current pathways inside the tissue as a result of differences in impedances between the semiconductor and the tissue. A cube substitution method using platinized conductive faces implanted in the tissue does not consider problems of alignment of the probes with the direction of isopotential lines or electrode-electrolyte impedance. Also, such electrodes measure only dc current. In a method using a three dimensional electrode to provide three-dimensional information, the author did not give evidence that these electrodes have a zero field distortion, and also did not give information about measurements made using his electrodes. None of the above methods provide a solid approach to the problems of measuring induced current densities. This thesis attempts to present a method of measuring induced current density. The method is capable of measuring both the magnitude and direction of induced current densities. It uses five point electrodes, four of them applied inside the tissue while the fifth one is just in electrical contact with the tissue. The method consists of a probe configuration system, an open-loop operational amplifier and a balanced semi-floating current driver. Leakage current, which goes to the ground and causes error, can be adjusted to be very low (about 0.01% of the total output current). A pair of Helmoltz coils was employed to provide a system for producing time-varying magnetic field. The core of the coil pair was shielded and grounded by a cut metal shield, to avoid any interference from time-varying electric field. The shield was also used as a metal incubator to keep biological samples at body temperature. The heat to the shield was supplied by a unit consisting of four power transistors, and a circuit of sensing, and controlling components. The method used in this study was tested by making measurements of eddy current densities induced in physiological saline solution as a model of a biological conducting fluid. The measurements were represented by arrows, each representing a single measurement, with the length of the arrow representing the magnitude of current density and the direction representing the direction of the induced current. Because electrically induced eddy currents are dependent on electric charge density available inside tissue, and therefore dependent on tissue electrical conductivity, this thesis presents a direct and simple method for measuring complex tissue electrical conductivity. The method uses the same five-electrode system and shares the same point electrode configurations and balanced semi-floating current driver as used for eddy current measurements. The method measures both real and imaginary components of tissue complex conductivity. Both systems are gathered into one box and their functions are separated by four toggle switches. Measurements of electrical induced current densities and complex electrical conductivities for body fluids and tissues have been carried out on saline solutions with different ionic concentrations, expired human whole blood, expired human plasma, human cerebrospinal fluid (CSF) and human urine. Solid tissue such as bovine cardiac muscle and liver were also examined. Current-to-field ratios were obtained for experiments in both fluid and tissues.

Thesis (M.A.)--Cleveland State University, 2007. / Abstract. Title from PDF t.p. (viewed on May 8, 2008). Includes bibliographical references (p. 56-63). Available online via the OhioLINK ETD Center. Also available in print.

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BACKGROUND: The Canadian healthcare system is subject to national standards that may be challenging to meet, given the evolution and integration of technology in healthcare in disciplines like functional neurosurgery, utilizing therapies such as deep brain stimulation (DBS), whereby implanted devices have provided benefit for patients with movement disorders. A comprehensive assessment of the need for this service to match with the delivery of DBS has not been performed. This thesis comprises a series of studies that aim to address this knowledge gap through the quadruple aim of health service research. METHODS: The first study is a systematic review and meta-analysis including economic evaluations comparing DBS for movement disorders with medical management only. The second is a mixed methods survey of Canadian stakeholders for DBS. The final study is a nationwide retrospective cohort study of DBS patients from 2019-2022 to determine factors that may influence access. RESULTS: Through analysis of 14 economic evaluations, DBS appears to be a cost-effective treatment when considered across the remaining lifespan of the patient with positive incremental net benefit for DBS with a mean difference of 40,504.81USD (95% CI 2,422.42; 78,587.19). Additionally, 220 responses from all DBS stakeholder groups revealed that costs associated with travel, waitlists, lack of specific resources, poor understanding of movement disorders and DBS indications, and referral pathways were barriers to accessing DBS. Finally, preliminary results identified 162 DBS patients. Potential factors that may increase access to DBS were indication (Parkinson’s disease), higher socioeconomic status, and race. CONCLUSIONS: While DBS is a cost-effective therapy for patients with movement disorders, the current delivery of this service needs significant improvement. This includes improved education, streamlined referral pathways, and policy change at a governmental level, with further investigation to determine regions of the country where need for DBS far exceeds current access. / Dissertation / Candidate in Philosophy / Movement disorders are progressive, debilitating neurologic conditions that severely impact the quality, speed and fluency of movement as a result of basal ganglia dysfunction. Medical therapies remain the mainstay of treatment, however high quality evidence supports the use of deep brain stimulation (DBS) to relieve these symptoms in well-selected patients. Given the upfront cost of surgery associated with DBS, and the comprehensive evaluations at tertiary care centres (including a multidisciplinary team with neurologists, neurosurgeons, neuropsychologists, psychiatrists, and electrophysiologists), this is a limited resource, particularly in overburdened publicly funded healthcare systems. There have been no previous attempts to comprehensively analyze access to DBS in Canada’s public healthcare system through investigation of need for these services, matched access, and investigation of barriers to access. This thesis comprises 5 chapters that inform this knowledge gap through the quadruple aim of health service research (patient perspective, health care provider perspective, cost, and population level data), aiming for equitable access to care in Canada. Chapter 1 is an introduction providing the rationale for conducting each of the included studies. Chapter 2 reports on an evaluation of cost, titled Economic Evaluations Comparing Deep Brain Stimulation to Best Medical Therapy for Movement Disorders: A Meta-Analysis. Chapter 3 presents an evaluation of healthcare provider and patient perspective, titled Mixed Methods Survey of Stakeholders to Identify Barriers to Accessing Deep Brain Stimulation for Movement Disorders in Canada. Chapter 4 is a retrospective cohort study providing population level data assessing patients who have received DBS in Canada, titled Canadian Access to Deep Brain Stimulation for Movement Disorders: A Nationwide Retrospective Study. Finally, Chapter 5 discusses the conclusion, limitations, and implications of the research presented in this PhD thesis.