RESUMO
INTRODUCTION: Many experts assume bilateral deep brain stimulation (DBS) is necessary to improve axial tremor in essential tremor (ET). In the largest clinical trial of DBS for ET to date evaluating a non-directional, constant current device, we studied the effects of unilateral and staged bilateral DBS on axial tremor. METHODS: We included all participants from the original trial with unilateral ventral intermediate nucleus (VIM) DBS and 90-day follow up at minimum. Primary outcomes were changes in pooled axial subscores in the Clinical Rating Scale for Tremor (CRST) at 90 and 180 days after activation of unilateral VIM DBS compared to pre-operative baseline (n=119). Additionally, we performed within-subject analyses for unilateral versus bilateral DBS at 180 days in the cohort who underwent staged surgery to bilateral DBS (n=39). RESULTS: Unilateral VIM DBS improved midline tremor by 58% at 90 days (median[IQR]) (3[3] to 1[2], p<0.001) and 65% at 180 days (3[3] to 1[2], p<0.001) versus pre-op baseline. In the staged to bilateral DBS cohort, midline tremor scores further improved after bilateral DBS at 180 days by 63% versus unilateral DBS (3[3] to 1[3], p=0.007). There were, however, 35 additional DBS and surgery-related adverse events, 14 related to incoordination, gait impairment, or speech impairment, versus 6 after unilateral DBS. CONCLUSION: Unilateral VIM DBS for ET significantly improved associated axial tremor. Staged bilateral DBS was associated with additional axial tremor improvement but also additional adverse events. Unilateral VIM DBS may be sufficient to achieve a goal of contralateral limb and axial tremor attenuation.
Assuntos
Estimulação Encefálica Profunda/métodos , Tremor Essencial/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde , Núcleos Ventrais do Tálamo , Idoso , Estimulação Encefálica Profunda/efeitos adversos , Tremor Essencial/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: This study of thalamic deep brain stimulation (DBS) investigated whether a novel constant-current device improves tremor and activities of daily living (ADL) in patients with essential tremor (ET). METHODS: A prospective, controlled, multicenter study was conducted at 12 academic centers. We investigated the safety and efficacy of unilateral and bilateral constant-current DBS of the ventralis intermedius (VIM) nucleus of the thalamus in patients with essential tremor whose tremor was inadequately controlled by medications. The primary outcome measure was a rater-blinded assessment of the change in the target limb tremor score in the stimulation-on versus stimulation-off state six months following surgery. Multiple secondary outcomes were assessed at one-year follow-up, including motor, mood, and quality-of-life measures. RESULTS: 127 patients were implanted with VIM DBS. The blinded, primary outcome variable (n = 76) revealed a mean improvement of 1.25 ± 1.26 points in the target limb tremor rating scale (TRS) score in the arm contralateral to DBS (p < 0.001). Secondary outcome variables at one year revealed significant improvements (p ≤ 0.001) in quality of life, depression symptoms, and ADL scores. Forty-seven patients had a second contralateral VIM-DBS, and this group demonstrated reduction in second-sided tremor at 180 days (p < 0.001). Serious adverse events related to the surgery included infection (n = 3), intracranial hemorrhage (n = 3), and device explantation (n = 3). CONCLUSION: Unilateral and bilateral constant-current VIM DBS significantly improves upper extremity tremor, ADL, quality of life, and depression in patients with severe ET.
Assuntos
Estimulação Encefálica Profunda , Tremor Essencial/terapia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/instrumentação , Estimulação Encefálica Profunda/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Tálamo , Resultado do TratamentoRESUMO
Restless legs syndrome (RLS) is a disorder characterized by an irresistible urge to move the legs during rest, usually accompanied by uncomfortable sensations in the affected extremity or extremities. RLS can manifest at any age but prevalence increases with advancing age. This article describes the symptoms of RLS, associated comorbidities, and how to diagnose and manage RLS.
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Síndrome das Pernas Inquietas , Humanos , Prevalência , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/terapiaRESUMO
BACKGROUND: The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus. METHODS: This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474. FINDINGS: Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87-4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. INTERPRETATION: Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. FUNDING: St Jude Medical Neuromodulation Division.
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Estimulação Encefálica Profunda/métodos , Doença de Parkinson/terapia , Idoso , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/instrumentação , Discinesias/terapia , Eletrodos Implantados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Estudos Prospectivos , Índice de Gravidade de Doença , Núcleo Subtalâmico/cirurgia , Resultado do TratamentoRESUMO
Selegiline is a monoamine-B specific inhibitor used to treat Parkinson's disease. A Zydis sublingual preparation has more efficient absorption and less first pass amphetamine metabolites. We conducted an open label oral to Zydis switch study to evaluate tolerability of rapid switch, and relative efficacy, in 48 subjects from 5 sites. Overall patients preferred the Zydis preparation. Per clinician global impressions, fluctuations improved and the "on" UPDRS part II scores improved. Total UPDRS and measures of fatigue and sleep were unchanged. Adverse events were mild. Patients generally preferred the Zydis selegiline preparation but the modest difference is of unclear clinical significance given the open label nature of the trial.
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Substituição de Medicamentos , Doença de Parkinson/tratamento farmacológico , Selegilina/administração & dosagem , Selegilina/efeitos adversos , Administração Oral , Administração Sublingual , Idoso , Química Farmacêutica , Substituição de Medicamentos/métodos , Feminino , Seguimentos , Humanos , Masculino , Doença de Parkinson/metabolismo , Resultado do TratamentoRESUMO
Previous electrophysiological studies of the basal ganglia in Parkinson's 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.
RESUMO
Previous electrophysiological studies of the basal ganglia in Parkinson's 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.
Assuntos
Gânglios da Base/fisiopatologia , Neurônios/fisiologia , Doença de Parkinson/fisiopatologia , Potenciais de Ação , Globo Pálido/fisiopatologia , Humanos , Teoria da Informação , Modelos Lineares , Núcleo Subtalâmico/fisiopatologiaRESUMO
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 = 197) 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.
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Testes Neuropsicológicos , Doença de Parkinson/patologia , Análise e Desempenho de Tarefas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The glutamatergic system is thought to contribute to the motor disturbances observed in Parkinson's disease. Blockade of glutamatergic activity by a selective antagonist of the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor is associated with improvement in motor symptoms in a preclinical model of Parkinson's disease. A randomized, double-blind, double-dummy, placebo-controlled, 3-period crossover study was conducted in patients with moderate Parkinson's disease to evaluate the pharmacologic activity of MK-0657, an NR2B-selective NMDA receptor antagonist. Patients (n=16) received single oral doses of MK-0657 7 mg, carbidopa/levodopa 25/250 mg (LD) as a positive control, and placebo, after which motor function was serially evaluated by means of the Unified Parkinson's Disease Rating Scale-Motor Examination (UPDRS-ME). LD administration resulted in significant improvement in the UPDRS-ME relative to placebo (P=.025), confirming the sensitivity of the test paradigm; however, the UPDRS-ME change following MK-0657 administration showed no improvement compared with placebo (P=.110) despite exceeding the target MK-0657 plasma concentration of 400 nM. Although the administration of MK-0657 was generally well tolerated, it was associated with increases in systolic and diastolic blood pressure relative to placebo. The results of this study do not support ongoing clinical development of MK-0657 as a novel monotherapy for Parkinson's disease.
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Antiparkinsonianos/uso terapêutico , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Idoso , Carbidopa/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/induzido quimicamente , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
Parkinson's 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.
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Diagnóstico por Computador/métodos , Internet , Doença de Parkinson/diagnóstico , Software , Inquéritos e Questionários , Telemedicina/métodos , Interface Usuário-Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
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.
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Força da Mão , Contração Isométrica/fisiologia , Atividade Motora , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/fisiopatologia , Tremor/fisiopatologia , Adulto , Doença de Alzheimer/fisiopatologia , Avaliação da Deficiência , Dedos/fisiologia , Mãos/fisiologia , Humanos , Programas de Rastreamento , Doença de Parkinson/fisiopatologia , Valores de ReferênciaRESUMO
A number of clinical and research situations arise that require the integration of complex, multi-dimensional, performance-related information to determine a single quantity such as "disease severity" or "risk level" (for subsequent development of a disease). This process is generally carried out either by relying on a subjective gestalt approach or by using rating scales that combine scores for component measures using an additive process without justification. Concepts from general systems performance theory have provided insights into this problem, teaching that a fundamentally multiplicative method of integrating components is often appropriate. In this paper, concepts and previous supportive experimental work are reviewed in the context of the quantitative characterization of disease severity. A Parkinson's disease study (n=114) is presented that mimics the "two-condition" situation encountered in the clinical trial of a new drug or other therapy. Traditional and performance theory-based composite scores are computed for each condition ("on" and "off" medications) and compared, with emphasis on the different quantitative "pictures" conveyed by each approach. It is concluded that performance theory based composites are not only more sensitive to therapeutic agents experimentally, but also have superior conceptual validity compared to traditional forms of single-number composites.
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Doença de Parkinson/fisiopatologia , Índice de Gravidade de Doença , Antiparkinsonianos/uso terapêutico , Sistemas de Gerenciamento de Base de Dados , Humanos , Doença de Parkinson/tratamento farmacológico , Projetos de Pesquisa , Medição de RiscoRESUMO
High-frequency stimulation of the subthalamic nucleus is a neurosurgical procedure for the alleviation of motor symptoms of Parkinson's 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.
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Estimulação Encefálica Profunda/métodos , Doença de Parkinson , Cuidados Pós-Operatórios/métodos , Núcleo Subtalâmico/cirurgia , Anestesiologia , Antiparkinsonianos/uso terapêutico , Terapia Combinada , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/enfermagem , Desenho de Equipamento , Família/psicologia , Humanos , Destreza Motora , Neurofisiologia , Neurocirurgia , Profissionais de Enfermagem/organização & administração , Doença de Parkinson/reabilitação , Doença de Parkinson/cirurgia , Equipe de Assistência ao Paciente/organização & administração , Seleção de Pacientes , Medicina Física e Reabilitação , Cuidados Pós-Operatórios/enfermagem , Texas , Resultado do TratamentoRESUMO
Parkinson's 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.