Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton.

Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation and antigravity assistance augments upper limb function and brain activity during rehabilitation exercises and may thus provide a novel restorative framework for severely affected stroke patients.

Intraductal papilloma of the male breast.

We report the case of a 29-year-old male patient who presented with a painless lump of his left breast that was found to be an intraductal papilloma. This is an extremely rare, but benign disease in the male breast. We subsequently discuss radiologic tests and treatment options.

Decoding upper limb residual muscle activity in severe chronic stroke.

OBJECTIVE: Stroke is a leading cause of long-term motor disability. Stroke patients with severe hand weakness do not profit from rehabilitative treatments. Recently, brain-controlled robotics and sequential functional electrical stimulation allowed some improvement. However, for such therapies to succeed, it is required to decode patients' intentions for different arm movements. Here, we evaluated whether residual muscle activity could be used to predict movements from paralyzed joints in severely impaired chronic stroke patients. METHODS: Muscle activity was recorded with surface-electromyography (EMG) in 41 patients, with severe hand weakness (Fugl-Meyer Assessment [FMA] hand subscores of 2.93 ± 2.7), in order to decode their intention to perform six different motions of the affected arm, required for voluntary muscle activity and to control neuroprostheses. Decoding of paretic and nonparetic muscle activity was performed using a feed-forward neural network classifier. The contribution of each muscle to the intended movement was determined. RESULTS: Decoding of up to six arm movements was accurate (>65%) in more than 97% of nonparetic and 46% of paretic muscles. INTERPRETATION: These results demonstrate that some level of neuronal innervation to the paretic muscle remains preserved and can be used to implement neurorehabilitative treatments in 46% of patients with severe paralysis and extensive cortical and/or subcortical lesions. Such decoding may allow these patients for the first time after stroke to control different motions of arm prostheses through muscle-triggered rehabilitative treatments.

[A paradox: sarcoidosis in an HIV-positive patient]. / Een paradox: sarcoïdose bij een hiv-positieve patiënt.

BACKGROUND: In view of the diminished number of CD4+ lymphocytes, the co-existence of an HIV infection and sarcoidosis seems paradoxical. Immune reconstitution inflammatory syndrome (IRIS) may be observed in response to anti-retroviral therapy (ART). According to the conventional definition, this is caused by an overwhelming immune response to an already present or to a new agent. CASE DESCRIPTION: We describe the case of a 47-year-old HIV-positive patient, who presented with an exacerbation of his sarcoidosis nine months after initiation of ART. Based on the time course and the dynamics of the CD4+ lymphocyte count, this presentation of disease can be placed in the context of IRIS. CONCLUSION: The presentation or exacerbation of sarcoidosis after initiation of antiretroviral therapy in HIV-positive patients with a low CD4+ count at start of therapy can be placed in the context of IRIS.

Learned self-regulation of the lesioned brain with epidural electrocorticography.

INTRODUCTION: Different techniques for neurofeedback of voluntary brain activations are currently being explored for clinical application in brain disorders. One of the most frequently used approaches is the self-regulation of oscillatory signals recorded with electroencephalography (EEG). Many patients are, however, unable to achieve sufficient voluntary control of brain activity. This could be due to the specific anatomical and physiological changes of the patient's brain after the lesion, as well as to methodological issues related to the technique chosen for recording brain signals. METHODS: A patient with an extended ischemic lesion of the cortex did not gain volitional control of sensorimotor oscillations when using a standard EEG-based approach. We provided him with neurofeedback of his brain activity from the epidural space by electrocorticography (ECoG). RESULTS: Ipsilesional epidural recordings of field potentials facilitated self-regulation of brain oscillations in an online closed-loop paradigm and allowed reliable neurofeedback training for a period of 4 weeks. CONCLUSION: Epidural implants may decode and train brain activity even when the cortical physiology is distorted following severe brain injury. Such practice would allow for reinforcement learning of preserved neural networks and may well provide restorative tools for those patients who are severely afflicted.

From assistance towards restoration with epidural brain-computer interfacing.

PURPOSE: Today's implanted brain-computer interfaces make direct contact with the brain or even penetrate the tissue, bearing additional risks with regard to safety and stability. What is more, these approaches aim to control prosthetic devices as assistive tools and do not yet strive to become rehabilitative tools for restoring lost motor function. METHODS: We introduced a less invasive, implantable interface by applying epidural electrocorticography in a chronic stroke survivor with a persistent motor deficit. He was trained to modulate his natural motor-related oscillatory brain activity by receiving online feedback. RESULTS: Epidural recordings of field potentials in the beta-frequency band projecting onto the anatomical hand knob proved most successful in discriminating between the attempt to move the paralyzed hand and to rest. These spectral features allowed for fast and reliable control of the feedback device in an online closed-loop paradigm. Only seven training sessions were required to significantly improve maximum wrist extension. CONCLUSIONS: For patients suffering from severe motor deficits, epidural implants may decode and train the brain activity generated during attempts to move with high spatial resolution, thus facilitating specific and high-intensity practice even in the absence of motor control. This would thus transform them from pure assistive devices to restorative tools in the context of reinforcement learning and neurorehabilitation.

Epidural electrocorticography of phantom hand movement following long-term upper-limb amputation.

INTRODUCTION: Prostheses for upper-limb amputees are currently controlled by either myoelectric or peripheral neural signals. Performance and dexterity of these devices is still limited, particularly when it comes to controlling hand function. Movement-related brain activity might serve as a complementary bio-signal for motor control of hand prosthesis. METHODS: We introduced a methodology to implant a cortical interface without direct exposure of the brain surface in an upper-limb amputee. This bi-directional interface enabled us to explore the cortical physiology following long-term transhumeral amputation. In addition, we investigated neurofeedback of electrocorticographic brain activity related to the patient's motor imagery to open his missing hand, i.e., phantom hand movement, for real-time control of a virtual hand prosthesis. RESULTS: Both event-related brain activity and cortical stimulation revealed mutually overlapping cortical representations of the phantom hand. Phantom hand movements could be robustly classified and the patient required only three training sessions to gain reliable control of the virtual hand prosthesis in an online closed-loop paradigm that discriminated between hand opening and rest. CONCLUSION: Epidural implants may constitute a powerful and safe alternative communication pathway between the brain and external devices for upper-limb amputees, thereby facilitating the integrated use of different signal sources for more intuitive and specific control of multi-functional devices in clinical use.

Spatial filtering based on canonical correlation analysis for classification of evoked or event-related potentials in EEG data.

Classification of evoked or event-related potentials is an important prerequisite for many types of brain-computer interfaces (BCIs). To increase classification accuracy, spatial filters are used to improve the signal-to-noise ratio of the brain signals and thereby facilitate the detection and classification of evoked or event-related potentials. While canonical correlation analysis (CCA) has previously been used to construct spatial filters that increase classification accuracy for BCIs based on visual evoked potentials, we show in this paper, how CCA can also be used for spatial filtering of event-related potentials like P300. We also evaluate the use of CCA for spatial filtering on other data with evoked and event-related potentials and show that CCA performs consistently better than other standard spatial filtering methods.

Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation.

Motor recovery after stroke is an unsolved challenge despite intensive rehabilitation training programs. Brain stimulation techniques have been explored in addition to traditional rehabilitation training to increase the excitability of the stimulated motor cortex. This modulation of cortical excitability augments the response to afferent input during motor exercises, thereby enhancing skilled motor learning by long-term potentiation-like plasticity. Recent approaches examined brain stimulation applied concurrently with voluntary movements to induce more specific use-dependent neural plasticity during motor training for neurorehabilitation. Unfortunately, such approaches are not applicable for the many severely affected stroke patients lacking residual hand function. These patients require novel activity-dependent stimulation paradigms based on intrinsic brain activity. Here, we report on such brain state-dependent stimulation (BSDS) combined with haptic feedback provided by a robotic hand orthosis. Transcranial magnetic stimulation (TMS) of the motor cortex and haptic feedback to the hand were controlled by sensorimotor desynchronization during motor-imagery and applied within a brain-machine interface (BMI) environment in one healthy subject and one patient with severe hand paresis in the chronic phase after stroke. BSDS significantly increased the excitability of the stimulated motor cortex in both healthy and post-stroke conditions, an effect not observed in non-BSDS protocols. This feasibility study suggests that closing the loop between intrinsic brain state, cortical stimulation and haptic feedback provides a novel neurorehabilitation strategy for stroke patients lacking residual hand function, a proposal that warrants further investigation in a larger cohort of stroke patients.

Coupling BCI and cortical stimulation for brain-state-dependent stimulation: methods for spectral estimation in the presence of stimulation after-effects.

Brain-state-dependent stimulation (BSDS) combines brain-computer interfaces (BCIs) and cortical stimulation into one paradigm that allows the online decoding for example of movement intention from brain signals while simultaneously applying stimulation. If the BCI decoding is performed by spectral features, stimulation after-effects such as artefacts and evoked activity present a challenge for a successful implementation of BSDS because they can impair the detection of targeted brain states. Therefore, efficient and robust methods are needed to minimize the influence of the stimulation-induced effects on spectral estimation without violating the real-time constraints of the BCI. In this work, we compared four methods for spectral estimation with autoregressive (AR) models in the presence of pulsed cortical stimulation. Using combined EEG-TMS (electroencephalography-transcranial magnetic stimulation) as well as combined electrocorticography (ECoG) and epidural electrical stimulation, three patients performed a motor task using a sensorimotor-rhythm BCI. Three stimulation paradigms were varied between sessions: (1) no stimulation, (2) single stimulation pulses applied independently (open-loop), or (3) coupled to the BCI output (closed-loop) such that stimulation was given only while an intention to move was detected using neural data. We found that removing the stimulation after-effects by linear interpolation can introduce a bias in the estimation of the spectral power of the sensorimotor rhythm, leading to an overestimation of decoding performance in the closed-loop setting. We propose the use of the Burg algorithm for segmented data to deal with stimulation after-effects. This work shows that the combination of BCIs controlled with spectral features and cortical stimulation in a closed-loop fashion is possible when the influence of stimulation after-effects on spectral estimation is minimized.

[Eosinophilia and a solid tumour: ovarian sarcoma]. / Eosinofilie bij een solide tumor: ovariumsarcoom.

A 50-year-old woman developed blood eosinophilia during admission to hospital in connection with abdominal symptoms. Eosinophilia is associated with a broad variety of diseases. The major causes of eosinophilia, i.e. an allergic reaction, a parasitic infection and a haematological malignancy, were ruled out. An ultrasound of the abdomen showed a large tumour in the lower abdomen which, because of the patient's history, was attributed to a uterine myoma. Later, this tumour proved to be a mesenchymal malignancy, and surgery was performed to remove it. Histopathology confirmed a high grade sarcoma which had its origin in the right ovary. It is known that eosinophilia can be a paraneoplastic sign of several carcinomas, but it has only infrequently been described in sarcomas. The pathophysiology of tumour-associated eosinophilia is unknown.