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Magnetic resonance guided high intensity focused ultrasound is a novel, non-invasive, image-guided procedure that is able to ablate intracranial tissue with submillimetre precision. It is currently FDA approved for essential tremor and tremor dominant Parkinson's disease. The aim of this update is to review the limitations of current landmark-based targeting techniques of the ventral intermediate nucleus and demonstrate the role of emerging imaging techniques that are relevant for both magnetic resonance guided high intensity focused ultrasound and deep brain stimulation. A significant limitation of standard MRI sequences is that the ventral intermediate nucleus, dentatorubrothalamic tract, and other deep brain nuclei cannot be clearly identified. This paper provides original, annotated images demarcating the ventral intermediate nucleus, dentatorubrothalamic tract, and other deep brain nuclei on advanced MRI sequences such as fast grey matter acquisition T1 inversion recovery, quantitative susceptibility mapping, susceptibility weighted imaging, and diffusion tensor imaging tractography. Additionally, the paper reviews clinical efficacy of targeting with these novel MRI techniques when compared to current established landmark-based targeting techniques. The paper has widespread applicability to both deep brain stimulation and magnetic resonance guided high intensity focused ultrasound.
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Temblor Esencial/diagnóstico por imagen , Temblor Esencial/terapia , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Imagen por Resonancia Magnética/métodos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/terapia , Estimulación Encefálica Profunda/métodos , Globo Pálido/diagnóstico por imagen , HumanosAsunto(s)
Becas , Trastornos del Movimiento , Humanos , Trastornos del Movimiento/terapia , Sociedades MédicasAsunto(s)
COVID-19 , Educación a Distancia , Trastornos del Movimiento , Humanos , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Introduction: Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD) that can significantly improve motor symptoms and quality of life. Despite its effectiveness, little is known about patient perceptions of DBS. Objectives: To evaluate patient perceptions of DBS for PD, focusing on understanding, satisfaction, and factors influencing their outlook. This study aims to enhance patient education and counseling by identifying key determinants of patient perceptions. Design: A patient survey. Methods: We surveyed 77 PD patients who had undergone DBS at multiple centers using a comprehensive questionnaire. The questionnaire included questions on demographic information, disease history, and detailed understanding about the indications for DBS, side effects, outlook, and other common misconceptions. We summarize data using measures of central tendency and dispersion appropriate to the data type (categorical, continuous, proportional) and model relationships among variables using fractional and linear regression methods. Results: Participants had a median age of 66 years, were predominantly male (66%), Caucasian (90%), well-educated (79% with at least college degrees), and had a disease duration of greater than 5 years (97%). They conveyed good understanding of the signs and symptoms addressed by DBS across the motor and non-motor domains and associated side effects. Regression analysis identified age, disease duration, and education level as key determinants of patient understanding and outlook of DBS. Conclusion: Our study provides a detailed understanding of patient perceptions of DBS for PD, including the benefits, challenges, and misconceptions. Our findings underscore the importance of identifying the causes of disparities in patient knowledge and perceptions regarding DBS to tailor patient counseling and ensure optimal treatment outcomes.
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BACKGROUND: Early onset Parkinson's disease (EOPD) affects people in the prime of their lives, typically between 21 and 50 years of age, which results in a variety of challenges that are unique compared to those diagnosed later in life. A better understanding of the unmet needs of this population is critical to delivering bespoke care and improving their quality of life. OBJECTIVES: To assess the unmet needs of people with early onset Parkinson's disease. METHODS: A cross-sectional sample of 198 adults with self-identified early onset Parkinson's disease completed surveys to ascertain the most common unmet needs of this population. Simple descriptive statistics including frequencies, means, and standard deviations were used to quantify the most common unmet needs and were compared between men, women, and Hispanic/Latino with significance determined by chi-square tests. RESULTS: Overall, the top five unmet needs were (1) need for "a community more like me" (65.2%), (2) more PD information (48%), (3) information about how their PD will progress (47%), (4) help with mental health issues (34.8%), and (5) help with employment issues (33.8%). The top unmet need for men was help with employment issues (50.8%), for women, "a community more like me" (72.3%), and for Hispanic/Latinos, more PD information (47%). CONCLUSION: Although the number of people living with EOPD is considerably smaller than those with conventional age at onset, the potential impact to quality of life in this population remains tremendous. We propose a framework to start to address these needs.
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Enfermedad de Parkinson , Masculino , Adulto , Humanos , Femenino , Enfermedad de Parkinson/diagnóstico , Estudios Transversales , Calidad de Vida , Encuestas y Cuestionarios , Edad de InicioRESUMEN
Background and Objectives: Parkinson disease (PD) and progressive supranuclear palsy (PSP) are often difficult to differentiate in the clinic. The MR parkinsonism index (MRPI) has been recommended to assist in making this distinction. We aimed to assess the usefulness of this tool in our real-world practice of movement disorders. Methods: We prospectively obtained MRI scans on consecutive patients with movement disorders with a clinical indication for imaging and obtained measures of MRI regions of interest (ROIs) from our neuroradiologists. The authors reviewed all MRI scans and corrected any errors in the original ROI drawings for this analysis. We retrospectively assigned diagnoses using established consensus criteria from progress notes stored in our electronic medical record. We analyzed the data using multinomial logistic regression models and receiver operating curve analysis to determine the predictive accuracy of the MRI ratios. Results: MRI measures and consensus diagnoses were available on 130 patients with PD, 54 with PSP, and 77 diagnosed as other. The out-of-sample prediction error rate of our 5 regression models ranged from 45% to 59%. The average sensitivity and specificity of the 5 models in the testing sample were 53% and 80%, respectively. The positive predictive value of an MRPI ≥13.55 (the published cutoff) in our patients was 79%. Discussion: These results indicate that MRI measures of brain structures were not effective at predicting diagnosis in individual patients. We conclude that the search for a biomarker that can differentiate PSP from PD must continue.
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BACKGROUND: When rotigotine patch was withdrawn from the US market, we prospectively gathered data on efficacy, side effects, and daytime sedation on patients while taking rotigotine and following the switch to alternate therapies. METHODS: Patients rated the efficacy of rotigotine on a scale of 0-5 (ineffective to extremely effective) and completed the Epworth Sleepiness Scale. At a follow-up visit a mean of 3 months later, patients rated their change in efficacy and side effects on a scale of -3 to +3 (much worse to much better) and again completed the Epworth Sleepiness Scale. RESULTS: Thirty-three patients were switched to a single alternate treatment. On rotigotine, the average efficacy score was 3.5, and after switching, the average change in efficacy was -0.67 (worsening). Average change scores for efficacy and adverse effects were 0.25 and 0.38 for levodopa, -0.88 and -0.25 for ropinirole IR, -1.2 and -0.83 for ropinirole XL, -0.80 and 1.0 for pramipexole, and -1.0 and 0.50 for rasagiline, respectively. Average change in Epworth score on each alternate agent was -3.9, -2.3, 1.3, 3.0, and 1. CONCLUSION: Rotigotine was an effective treatment with all groups deteriorating after switch except for the levodopa group. Fifty-eight percent of patients preferred rotigotine versus 36% preferring the alternate treatment.
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Antiparkinsonianos/administración & dosificación , Trastornos de Somnolencia Excesiva/tratamiento farmacológico , Agonistas de Dopamina/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Tetrahidronaftalenos/administración & dosificación , Tiofenos/administración & dosificación , Anciano , Antiparkinsonianos/efectos adversos , Trastornos de Somnolencia Excesiva/fisiopatología , Trastornos de Somnolencia Excesiva/prevención & control , Agonistas de Dopamina/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Estudios Prospectivos , Tetrahidronaftalenos/efectos adversos , Tiofenos/efectos adversosRESUMEN
INTRODUCTION: SPEAK OUT! with The LOUD Crowd is a standardized speech therapy program typically consisting of 12 one-on-one treatments and ongoing weekly group maintenance sessions for patients with dysarthria due to Parkinson's disease (PD). It is based upon the hypothesis that increased attention to speech, which is a goal-directed motor activity, may compensate for the impairment in automatic sequential motor behaviors often demonstrated in patients with PD. We present results on the 1-year response to treatment. METHODS: Forty individuals with idiopathic PD received SPEAK OUT! delivered in 12 one-on-one 40-min treatment sessions 3 times per week for four consecutive weeks in addition to ongoing group maintenance sessions called The LOUD Crowd. Evaluations occurred 3 times at baseline, within one and six weeks after completion of the SPEAK OUT! sessions (N = 40) and 1-year later (N = 35). Assessments included mean speech intensity and intonation from reading and monolog, the voice quality acoustic measure called cepstral peak prominence (CPP), and scores on the voice-related quality of life questionnaire. RESULTS: The significant improvements achieved in all outcome measures from baseline to completion of SPEAK OUT! were maintained 1-year later. Participation throughout the year in regular group maintenance sessions (The LOUD Crowd) was positively correlated with level of improvement at 1 year for all measures except patient perception of voice. CONCLUSIONS: These long-term data contribute evidence of the effectiveness of this speech therapy program for improving communication for individuals with PD and emphasize the importance of regular and ongoing group sessions to sustain therapeutic gains.
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Disartria , Enfermedad de Parkinson , Humanos , Disartria/diagnóstico , Disartria/etiología , Disartria/terapia , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/terapia , Entrenamiento de la Voz , Calidad de la Voz , Estudios de Seguimiento , Calidad de Vida , Resultado del TratamientoRESUMEN
Parkinson's disease (PD) results in progressively worsening gait and balance dysfunction that can be measured using computerized devices. We utilized the longitudinal database of the Parkinson's Disease Biomarker Program to determine if baseline gait and balance measures predict future rates of symptom progression. We included 230, 222, 164, and 177 PD subjects with 6, 12, 18, and 24 months of follow-up, respectively, and we defined progression as worsening of the following clinical parameters: MDS-UPDRS total score, Montreal Cognitive Assessment, PDQ-39 mobility subscale, levodopa equivalent daily dose, Schwab and England score, and global composite outcome. We developed ridge regression models to independently estimate how each gait or balance measure, or combination of measures, predicted progression. The accuracy of each ridge regression model was calculated by cross-validation in which 90% of the data were used to estimate the ridge regression model which was then tested on the 10% of data left out. While the models modestly predicted change in outcomes at the 6-month follow-up visit (accuracy in the range of 66-71%) there was no change in the outcome variables during this short follow-up (median change in MDS-UPDRS total score = 0 and change in LEDD = 0). At follow-up periods of 12, 18, and 24 months, the models failed to predict change (accuracy in the held-out sets ranged from 42 to 60%). We conclude that this set of computerized gait and balance measures performed at baseline is unlikely to help predict future disease progression in PD. Research scientists must continue to search for progression predictors to enhance the performance of disease modifying clinical trials.
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Purpose SPEAK OUT! and The LOUD Crowd is a standardized speech therapy program of 12 individual treatments combined with ongoing weekly group sessions for individuals with dysarthria due to Parkinson's disease (PD). The premise of this program is that individuals with PD must rely on goal-directed basal ganglia-cortical circuits to compensate for deficits in habitual, automatic control. The purpose of this study was to assess the outcome of this therapy program. Method Forty individuals with idiopathic PD received SPEAK OUT! in 12 individual 40-min sessions 3 times per week for 4 consecutive weeks and also participated in The LOUD Crowd. Assessments were conducted 3 times at baseline and then within 1 and 6 weeks after completion of the individual SPEAK OUT! sessions. Twenty-five adults without communication disorders were assessed on the same schedule. Acoustic outcome measures were mean intensity from reading and monologue, the prosody measures of standard deviation of intensity and frequency from reading and monologue, and the voice quality measure of cepstral peak prominence from reading. Patient perception of voice was also assessed with the Voice-Related Quality of Life. Results Posttherapy, mean intensity was greater and variation of frequency was larger in reading and monologue, while variation in intensity was larger in monologue but unchanged in reading. Cepstral peak prominence and Voice-Related Quality of Life scores were significantly higher (improved) after therapy. Conclusion These data contribute to evidence of the effectiveness of this program for hypokinetic dysarthria secondary to idiopathic PD and thus inform clinical practice in the selection among treatment options.
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Disartria , Enfermedad de Parkinson , Adulto , Disartria/diagnóstico , Disartria/etiología , Disartria/terapia , Humanos , Enfermedad de Parkinson/complicaciones , Calidad de Vida , Medición de la Producción del Habla , Calidad de la VozRESUMEN
BACKGROUND: As the 2nd most common neurodegenerative disorder, Parkinson's disease (PD) affects over 1 million Americans. Treatment is complex and may include pharmacotherapy, rehabilitative measures, and surgical intervention. A comprehensive understanding of the patient's perceptions about PD is a vital step towards improving health literacy and clinical outcomes. METHODS: KnowPD is a web-based survey with Likert responses for a cross-sectional, nonrandomized study to assess patients' knowledge of PD symptoms, medications, deep brain stimulation (DBS), rehabilitation, and other factors relevant to disease management. RESULTS: Of the 98 subjects surveyed, 90% agreed they had sufficient knowledge of PD. However, in this cohort, 82% incorrectly believed levodopa stops working as the disease progresses, 77% erroneously thought DBS improves balance and reduces falls, and, <50% could answer specific questions regarding the dosing of levodopa despite over 75% reporting managing their own medications. A majority of patients (84%) believed it was possible to live well with PD, correlating with their self-reported knowledge of the disease. Finally, patients selected electronic video (13.7%) and reading (20.0%) material, yearly symposia (20.0%), and lunch lectures (28.4%) as their preferred method of information delivery. CONCLUSION: Misconceptions are prevalent among PD patients, and these appear to be unrelated to gender, provider type, or education level. Identification and characterization of this knowledge gap is vital towards allocating patient education resources, and the findings described herein will form the basis for effective educational interventions.
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BACKGROUND: Little information is available on the official postgraduate and subspecialty training programs in movement disorders (MD) in Europe and North Africa. OBJECTIVE: To survey the accessible MD clinical training in these regions. METHODS: We designed a survey on clinical training in MD in different medical fields, at postgraduate and specialized levels. We assessed the characteristics of the participants and the facilities for MD care in their respective countries. We examined whether there are structured, or even accredited postgraduate, or subspecialty MD training programs in neurology, neurosurgery, internal medicine, geriatrics, neuroradiology, neuropediatrics, and general practice. Participants also shared their suggestions and needs. RESULTS: The survey was completed in 31/49 countries. Structured postgraduate MD programs in neurology exist in 20 countries; structured neurology subspecialty training exists in 14 countries and is being developed in two additional countries. Certified neurology subspecialty training was reported to exist in 7 countries. Recommended reading lists, printed books, and other materials are the most popular educational tools, while courses, lectures, webinars, and case presentations are the most popular learning formats. Mandatory activities and skills to be certified were not defined in 15/31 countries. Most participants expressed their need for a mandatory postgraduate MD program and for certified MD sub-specialization programs in neurology. CONCLUSION: Certified postgraduate and subspecialty training exists only in a minority of European countries and was not found in the surveyed Egypt and Tunisia. MD training should be improved in many countries.
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Acreditación/estadística & datos numéricos , Curriculum/estadística & datos numéricos , Educación de Postgrado en Medicina/estadística & datos numéricos , Trastornos del Movimiento , Neurología/educación , Neurología/estadística & datos numéricos , Egipto , Europa (Continente) , Encuestas de Atención de la Salud/estadística & datos numéricos , Humanos , TúnezRESUMEN
Parkinsonism is a syndrome characterized by a combination of cardinal features including resting tremor, bradykinesia, rigidity, and loss of postural reflexes. The most common presentation of parkinsonism is the idiopathic variety first described by James Parkinson in 1817 now known as Parkinson's disease (PD). This article focuses on identifying the different subtypes of PD, with the recognition that treatment approaches may differ depending on the initial presenting feature. It also addresses issues related to the recognition and treatment of nonmotor comorbidities of PD, such as autonomic dysfunction and neuropsychiatric problems including depression and dementia.
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Antiparkinsonianos/uso terapéutico , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Trastornos del Conocimiento/epidemiología , Trastornos Mentales/epidemiología , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Enfermedades del Sistema Nervioso Autónomo/terapia , Trastornos del Conocimiento/terapia , Comorbilidad , Resistencia a Medicamentos , Humanos , Trastornos Mentales/terapia , PrevalenciaRESUMEN
Restless legs syndrome (RLS) is a chronic neurological disorder associated with sleep disturbance. Ropinirole, a non-ergot dopamine agonist, has been widely studied for the treatment of moderate-to-severe primary RLS in a comprehensive clinical development program. In these studies, ropinirole was effective in significantly improving the symptoms of RLS, compared with placebo, in patients with moderate-to-severe primary RLS. These improvements are supported by data from individual studies, as well as by pooled analyses. Significant improvements in RLS symptoms were observed within 2 nights of treatment. Ropinirole also produced significant benefits on objective measures of RLS motor symptoms, such as periodic leg movements; and on subjective measures of sleep, ropinirole was generally well tolerated. A newly developed extended-release formulation of ropinirole may benefit patients who warrant an extended duration of therapy.
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Agonistas de Dopamina/uso terapéutico , Indoles/uso terapéutico , Síndrome de las Piernas Inquietas/tratamiento farmacológico , Ensayos Clínicos como Asunto , Agonistas de Dopamina/efectos adversos , Agonistas de Dopamina/farmacocinética , Agonistas de Dopamina/farmacología , Humanos , Indoles/efectos adversos , Indoles/farmacocinética , Indoles/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome de las Piernas Inquietas/epidemiología , Síndrome de las Piernas Inquietas/etiología , Síndrome de las Piernas Inquietas/fisiopatologíaRESUMEN
Sleep-wake disturbances are common non-motor manifestations in Parkinson Disease (PD). Complex pathophysiological changes secondary to neurodegeneration in combination with motor symptoms and dopaminergic medications contribute to development of sleep-wake disturbances. The management of sleep complaints in PD is important as this symptom can affect daily activities and impair quality of life. Deep brain stimulation (DBS) is an effective adjunctive therapy for management of motor symptoms in PD. However, its effect on non-motor symptoms including sleep-wake disturbances is not widely understood. In this article, we reviewed studies assessing the effect of DBS at various therapeutic targets on sleep-wake disturbances. Of the studies examining the role of DBS in sleep-wake disturbances, the effect of subthalamic nucleus stimulation is most widely studied and has shown improvement in sleep quality, sleep efficiency, and sleep duration. Although, studies investigating changes in sleep with stimulation of thalamus, globus pallidus interna, and pedunculopontine nucleus are limited, they support the potential for modulation of sleep-wake centers with DBS at these sites. The mechanism by which DBS at different anatomical targets affects sleep-wake disturbances in PD is unclear and may involves multiple factors, including improved motor symptoms, medication adjustment, and direct modulation of sleep-wake centers.
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Deep Brain Stimulation (DBS) has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi) and Subthalamic Nucleus (STN) are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patient's profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institute's DBS paradigm to ensure that patients receive the optimal therapy.
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Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT2A receptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics.
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Antipsicóticos/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Antipsicóticos/farmacología , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/uso terapéutico , Clozapina/farmacología , Clozapina/uso terapéutico , Humanos , Terapia Molecular Dirigida , Neurotransmisores/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Piperidinas/farmacología , Piperidinas/uso terapéutico , Trastornos Psicóticos/metabolismo , Trastornos Psicóticos/fisiopatología , Fumarato de Quetiapina/farmacología , Fumarato de Quetiapina/uso terapéutico , Urea/análogos & derivados , Urea/farmacología , Urea/uso terapéuticoRESUMEN
DBS is a typically well-tolerated operation for treatment of Parkinson's disease, dystonia, and essential tremor (ET). Complications related to the surgical procedure and implanted hardware may occur. More commonly reported complications include hemorrhage, seizure, confusion, and infection. In this article, we report on a rare, but important, complication of DBS surgery, a brain cyst formation at the tip of the implanted ventralis intermedius nucleus (VIM) DBS lead in 2 patients who underwent the procedure at 2 different centers. The indication for surgery was debilitating ET, and in both cases, there was development of a delayed-onset neurological deficit associated with an internal capsule/thalamic cystic lesion formation located at the tip of the DBS lead. Case 1 presented within a few months post-DBS, whereas case 2 had a 10-mo delay to onset of symptoms. No clinical and radiological signs of infection were observed and both DBS systems were explanted with uneventful recovery.
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OBJECTIVE: To develop a process to improve patient outcomes from deep brain stimulation (DBS) surgery for Parkinson disease (PD), essential tremor (ET), and dystonia. METHODS: We employed standard quality improvement methodology using the Plan-Do-Study-Act process to improve patient selection, surgical DBS lead implantation, postoperative programming, and ongoing assessment of patient outcomes. RESULTS: The result of this quality improvement process was the development of a neuromodulation network. The key aspect of this program is rigorous patient assessment of both motor and non-motor outcomes tracked longitudinally using a REDCap database. We describe how this information is used to identify problems and to initiate Plan-Do-Study-Act cycles to address them. Preliminary outcomes data is presented for the cohort of PD and ET patients who have received surgery since the creation of the neuromodulation network. CONCLUSIONS: Careful outcomes tracking is essential to ensure quality in a complex therapeutic endeavor like DBS surgery for movement disorders. The REDCap database system is well suited to store outcomes data for the purpose of ongoing quality assurance monitoring.
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Estimulación Encefálica Profunda , Distonía/cirugía , Temblor Esencial/cirugía , Enfermedad de Parkinson/cirugía , Mejoramiento de la Calidad , Cognición , Humanos , Evaluación de Resultado en la Atención de Salud , Periodo PosoperatorioRESUMEN
In vitro exposure of murine bone marrow cells to increasing concentrations of zidovudine (AZT, 0.1-50 microM) had a concentration dependent suppressive effect on the growth of granulocyte-monocyte colony forming unit (CFU-GM) derived colonies. In our previous published study, the mechanism of AZT-induced suppression of erythroid colony forming unit (CFU-E) derived colonies was linked to a decrease in erythropoitin receptor (Epo-R) gene expression. In this study, we have observed that AZT exposure also induced a concentration dependent suppressive effect (35-90%) on GM-CSF receptor type alpha (GM-CSFR alpha) gene expression. The suppression of GM-CSFR alpha mRNA expression was specific, since AZT caused a much lower decrease (15-22%) on the IL-3 receptor type alpha (IL-3R alpha) message level, and had an insignificant effect on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and c-myc message levels. Erythropoietin (Epo) therapy has been used for reversal of AZT induced erythroid toxicity. Exposure to increasing concentrations (10-500 U/ml) of GM-CSF was unable to override the suppressive effect of AZT on CFU-GM derived colonies, however, treatment in combination with IL-3 (10-250 U/ml) ameliorated the suppressive effects of AZT on CFU-GM and on GM-CSFR alpha and IL-3R alpha gene expression. These findings suggest a mechanism via which AZT may suppress granulocyte-monocyte specific differentiation in murine bone marrow cells. These data also suggest that a combination of GM-CSF and IL-3 may be a superior therapeutic intervention for AZT-induced neutropenia.