First-in-human demonstration of floating EMG sensors and stimulators wirelessly powered and operated by volume conduction.

BACKGROUND: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. METHODS: A proof-of-concept device, consisting of implantable thin-film electrodes and a nonimplantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. RESULTS: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. CONCLUSIONS: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.

Is Lyapunov exponent a reliable metric to detect dynamic stability in Parkinson's disease?

Idiopathic Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. It affects the nervous system, causing motor and non-motor symptomatology. However, its clinical diagnosis remains dependent on the expertise of clinicians, as perceptual clinical scales are often used. Gait stability is one of the most relevant motor signs in PD. Nonetheless, it is usually not reported or quantified, possibly due to its unclear meaning and the high variability of metrics used in the literature. This work aims to identify a reliable and objective indicator that clinicians can use to assess patients in realistic contexts. We focused on the Largest Lyapunov Exponent (LLE), being the most common metric used in previous research works to quantify gait stability. The short and long-term LLEs were calculated in a group of 34 healthy and 42 participants diagnosed with PD. The long-term LLE extracted from the chest, right arm and right foot sensors showed statistical differences between subjects with PD and healthy control (HC) subjects, showing that the HC subjects are more stable than PD patients, whereas the short-term LLE showed the opposite results. Further investigation is required to clarify the reliability of this metric to detect and rate gait stability in people affected with PD.Clinical Relevance- This study is the first step towards the identification of an objective methodology to assess gait stability in clinical settings. Achieving this goal will contribute to improve the understanding and support the diagnosis of gait disorders that cause gait stability problems.

Classification of Kinematic and Electromyographic Signals Associated with Pathological Tremor Using Machine and Deep Learning.

Peripheral Electrical Stimulation (PES) of afferent pathways has received increased interest as a solution to reduce pathological tremors with minimal side effects. Closed-loop PES systems might present some advantages in reducing tremors, but further developments are required in order to reliably detect pathological tremors to accurately enable the stimulation only if a tremor is present. This study explores different machine learning (K-Nearest Neighbors, Random Forest and Support Vector Machines) and deep learning (Long Short-Term Memory neural networks) models in order to provide a binary (Tremor; No Tremor) classification of kinematic (angle displacement) and electromyography (EMG) signals recorded from patients diagnosed with essential tremors and healthy subjects. Three types of signal sequences without any feature extraction were used as inputs for the classifiers: kinematics (wrist flexion-extension angle), raw EMG and EMG envelopes from wrist flexor and extensor muscles. All the models showed high classification scores (Tremor vs. No Tremor) for the different input data modalities, ranging from 0.8 to 0.99 for the f1 score. The LSTM models achieved 0.98 f1 scores for the classification of raw EMG signals, showing high potential to detect tremors without any processed features or preliminary information. These models may be explored in real-time closed-loop PES strategies to detect tremors and enable stimulation with minimal signal processing steps.

Prediction of Pathological Tremor Signals Using Long Short-Term Memory Neural Networks.

Previous implementations of closed-loop peripheral electrical stimulation (PES) strategies have provided evidence about the effect of the stimulation timing on tremor reduction. However, these strategies have used traditional signal processing techniques that only consider phase prediction and might not model the non-stationary behavior of tremor. Here, we tested the use of long short-term memory (LSTM) neural networks to predict tremor signals using kinematic data recorded from Essential Tremor (ET) patients. A dataset comprising wrist flexion-extension data from 12 ET patients was pre-processed to feed the predictors. A total of 180 models resulting from the combination of network (neurons and layers of the LSTM networks, length of the input sequence and prediction horizon) and training parameters (learning rate) were trained, validated and tested. Predicted tremor signals using LSTM-based models presented high correlation values (from 0.709 to 0.998) with the expected values, with a phase delay between the predicted and real signals below 15 ms, which corresponds approximately to 7.5% of a tremor cycle. The prediction horizon was the parameter with a higher impact on the prediction performance. The proposed LSTM-based models were capable of predicting both phase and amplitude of tremor signals outperforming results from previous studies (32--56% decreased phase prediction error compared to the out-of-phase method), which might provide a more robust PES-based closed-loop control applied to PES-based tremor reduction.

Intramuscular Stimulation of Muscle Afferents Attains Prolonged Tremor Reduction in Essential Tremor Patients.

This study proposes and clinically tests intramuscular electrical stimulation below motor threshold to achieve prolonged reduction of wrist flexion/extension tremor in Essential Tremor (ET) patients. The developed system consisted of an intramuscular thin-film electrode structure that included both stimulation and electromyography (EMG) recording electrodes, and a control algorithm for the timing of intramuscular stimulation based on EMG (closed-loop stimulation). Data were recorded from nine ET patients with wrist flexion/extension tremor recruited from the Gregorio Marañón Hospital (Madrid, Spain). Patients participated in two experimental sessions comprising: 1) sensory stimulation of wrist flexors/extensors via thin-film multichannel intramuscular electrodes; and 2) surface stimulation of the nerves innervating the same target muscles. For each session, four of these patients underwent random 60-s trials of two stimulation strategies for each target muscle: 1) selective and adaptive timely stimulation (SATS) - based on EMG of the antagonist muscle; and 2) continuous stimulation (CON) of target muscles. Two patients underwent SATS stimulation trials alone while the other three underwent CON stimulation trials alone in each session. Kinematics of wrist, elbow, and shoulder, together with clinical scales, were used to assess tremor before, right after, and 24 h after each session. Intramuscular SATS achieved, on average, 32% acute (during stimulation) tremor reduction on each trial, while continuous stimulation augmented tremorgenic activity. Furthermore, tremor reduction was significantly higher using intramuscular than surface stimulation. Prolonged reduction of tremor amplitude (24 h after the experiment) was observed in four patients. These results showed acute and prolonged (24 h) tremor reduction using a minimally invasive neurostimulation technology based on SATS of primary sensory afferents of wrist muscles. This strategy might open the possibility of an alternative therapeutic approach for ET patients.

Transmigrant impacted mandibular canines: a retrospective study of 15 cases.

BACKGROUND: Transmigration of mandibular canines across the midline is rare. The authors describe the clinical and radiologic characteristics of patients with transmigrant impacted mandibular canines. METHODS: The authors conducted a retrospective observational study of 14 patients with transmigrant canines. They diagnosed transmigrant canines in all of the patients on the basis of the clinical and radiological findings, and they obtained the data from the patients' case histories and panoramic radiographs. They considered a canine to be transmigrant when one-half or more of its length crossed the mandibular midline. RESULTS: There were 15 transmigrated canines in 14 patients aged 16 to 60 years. Primary canines were present in 10 cases. One case involved a pericoronal infection, two involved supernumerary teeth, one was associated with an odontoma, and in two a pericoronal radiolucency was seen that was compatible with a follicular cyst. Treatment consisted of surgical extraction for eight patients, and periodic clinical and radiologic follow-up visits for six patients. CONCLUSIONS: Radiographic examination is necessary to diagnose impacted transmigrant canines, among other anomalies. Surgical extraction is the treatment of choice for patients with transmigrant canines involving associated pathology. In some cases, the management of asymptomatic impaction can be limited to periodic clinical and follow-up visits. CLINICAL IMPLICATIONS: The absence of the permanent canine within the arch beyond the normal time of eruption suggests the presence of an impacted canine. A transmigrant canine may develop an associated pathology.

Leiomyoma of the hard palate: a case report.

Leiomyoma is a benign smooth muscle tumor that is very rarely located in the oral cavity. It is accepted that the smooth muscle giving rise to this tumor corresponds to the tunica media of the arteries. The tumor can develop at any age, with no clear gender predilection, and typically manifests as a slow-growing, asymptomatic lesion. The diagnosis is based on the histopathological study, with the use of specific staining techniques, including immunohistochemical markers. Treatment consists of complete resection of the lesion, with due safety margins. We present the case of a 57-year-old male with a tumor located for the previous four months in the region of the hard palate, adjacent to the left upper premolars. After surgical resection with safety margins, hematoxylin-eosin staining and immunohistochemical study confirmed the diagnosis of leiomyoma.

Leiomioma del paladar duro: informe de caso / Leiomyoma of the hard palate: a case report

El leiomioma es un tumor benigno del músculo liso muy poco frecuente a nivel de la cavidad bucal. Se acepta que la fuente de músculo liso originaria de este tumor es la túnica media de los vasos arteriales. Se trata de un tumor que puedeaparecer a cualquier edad, sin presentar una clara predilección por el sexo y normalmente lo hace en forma de tumoración asintomática de crecimiento lento. Su diagnóstico está basado en el estudio anatomopatológico, utilizándose tinciones específicas como podrían ser las técnicas de inmunohistoquímica. Su tratamiento consiste en la extirpación completa de la lesión con márgenes de seguridad. En este artículo se expone el caso de un paciente hombre de 57 años que presentaba una lesión en el paladar duro, adyacente a los premolares superiores del lado izquierdo, de 4 meses de evolución. Tras la exéresis quirúrgica con márgenesde seguridad de dicha lesión, se realizó su estudio anatomopatológico. La tinción con hematoxilina y eosina junto conel estudio inmunohistoquímico de la muestra confirmaron el diagnóstico de leiomioma

Leiomyoma is a benign smooth muscle tumor that is very rarely located in the oral cavity. It is accepted that the smoothmuscle giving rise to this tumor corresponds to the tunica media of the arteries. The tumor can develop at any age, withno clear gender predilection, and typically manifests as a slow-growing, asymptomatic lesion. The diagnosis is basedon the histopathological study, with the use of specific staining techniques, including immunohistochemical markers.Treatment consists of complete resection of the lesion, with due safety margins.We present the case of a 57-year-old male with a tumor located for the previous four months in the region of the hardpalate, adjacent to the left upper premolars. After surgical resection with safety margins, hematoxylin-eosin staining andimmunohistochemical study confirmed the diagnosis of leiomyoma