RESUMO
People with late-stage Parkinson's disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD.
Assuntos
Estimulação Encefálica Profunda , Transtornos Neurológicos da Marcha , Doença de Parkinson , Masculino , Animais , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/terapia , Marcha/fisiologia , Medula EspinalRESUMO
Objective. Technical advances in deep brain stimulation (DBS) are crucial to improve therapeutic efficacy and battery life. We report the potentialities and pitfalls of one of the first commercially available devices capable of recording brain local field potentials (LFPs) from the implanted DBS leads, chronically and during stimulation. The aim was to provide clinicians with well-grounded tips on how to maximize the capabilities of this novel device, both in everyday practice and for research purposes.Approach. We collected clinical and neurophysiological data of the first 20 patients (14 with Parkinson's disease (PD), five with dystonia, one with chronic pain) that received the Percept™ PC in our centres. We also performed tests in a saline bath to validate the recordings quality.Main results. The Percept PC reliably recorded the LFP of the implanted site, wirelessly and in real time. We recorded the most promising clinically useful biomarkers for PD and dystonia (beta and theta oscillations) with and without stimulation. Furthermore, we provide an open-source code to facilitate export and analysis of data. Critical aspects of the system are presently related to contact selection, artefact detection, data loss, and synchronization with other devices.Significance. New technologies will soon allow closed-loop neuromodulation therapies, capable of adapting stimulation based on real-time symptom-specific and task-dependent input signals. However, technical aspects need to be considered to ensure reliable recordings. The critical use by a growing number of DBS experts will alert new users about the currently observed shortcomings and inform on how to overcome them.
Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Artefatos , Encéfalo , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapiaRESUMO
Assessment of locomotion through simple tests such as timed up and go (TUG) or walking trials can provide valuable information for the evaluation of treatment and the early diagnosis of people with Parkinson's disease (PD). Common methods used in clinics are either based on complex motion laboratory settings or simple timing outcomes using stop watches. The goal of this paper is to present an innovative technology based on wearable sensors on-shoe and processing algorithm, which provides outcome measures characterizing PD motor symptoms during TUG and gait tests. Our results on ten PD patients and ten age-matched elderly subjects indicate an accuracy ± precision of 2.8 ± 2.4 cm/s and 1.3 ± 3.0 cm for stride velocity and stride length estimation compared to optical motion capture, with the advantage of being practical to use in home or clinics without any discomfort for the subject. In addition, the use of novel spatio-temporal parameters, including turning, swing width, path length, and their intercycle variability, was also validated and showed interesting tendencies for discriminating patients in ON and OFF states and control subjects.
Assuntos
Marcha/fisiologia , Monitorização Ambulatorial/instrumentação , Doença de Parkinson/fisiopatologia , Sapatos , Processamento de Sinais Assistido por Computador , Idoso , Algoritmos , Humanos , Pessoa de Meia-Idade , Monitorização Ambulatorial/métodos , Reprodutibilidade dos Testes , Caminhada/fisiologiaRESUMO
Parkinsonian tremor is among the most emblematic medical signs and is one of the cardinal manifestations of Parkinson's disease (PD). Its semiology has been extensively addressed by ancient and contemporary medical literature, but more attention has been dedicated to its medical treatment in the past than nowadays. Among the hundreds of studies performed to determine the value of medical and surgical approaches on motor and non motor signs of PD, only a minority specifically considered effect on tremor as an efficacy outcome. Current available guidelines for PD treatment include attempts to specifically address tremor treatment but stress the low level of evidences available. In these conditions, with its still poorly understood pathophysiological basis and variable clinical expression PD tremor treatment is a clinical challenge. Only surgery (lesion or high frequency stimulation) of discrete deep brain targets consistently provides symptomatic long lasting alleviation. Through revision of contemporary scientific evidence, the purpose of this paper is to offer a systematic pragmatic approach to symptomatic management of tremor as one of the distinctive signs of PD that may generate substantial disability.