The Laparoscopic Implantation of Neuroprosthesis Procedure Increases Leg Lean Mass in Individuals With Paraplegia Due To Traumatic Spinal Cord Injury.

OBJECTIVES: We hypothesized that the laparoscopic implantation of neuroprosthesis (LION) procedure would significantly alter the body composition of patients with chronic traumatic spinal cord injury (SCI). The objectives were to determine the effect of the LION procedure on lean mass (LM), fatty mass (FM), and bone mineral content (BMC) in patients with SCI. MATERIALS AND METHODS: Five consecutive patients underwent dual-energy x-ray absorptiometry scans before the LION procedure and at the one-year postoperative follow-up to determine changes in LM, FM, and BMC. Student paired t-test was used to determine significance. RESULTS: The patients gained 2506 ± 565 g of LM in the legs (p < 0.001), which was an 18% total increase in leg LM. Total body LM was significantly increased by 3523 ± 1048 g (p < 0.003). FM was unaffected, whereas total BMC showed a small but significant increase of 99 ± 42 g (p = 0.009). CONCLUSIONS: The LION procedure and subsequent neurostimulation procedures resulted in substantial increases in leg LM in patients with chronic traumatic SCI and paraplegia. A possible incremental effect on total BMC also was observed. Further studies are needed to confirm and expand these promising results.

The impact of interdisciplinarity and user involvement on the design and usability of an assistive upper limb exoskeleton - a case study on the EXOTIC.

This study describes an interdisciplinary approach to develop a 5 degrees of freedom assistive upper limb exoskeleton (ULE) for users with severe to complete functional tetraplegia. Four different application levels were identified for the ULE ranging from basic technical application to interaction with users, interaction with caregivers and interaction with the society, each level posing requirements for the design and functionality of the ULE. These requirements were addressed through an interdisciplinary collaboration involving users, clinicians and researchers within social sciences and humanities, mechanical engineering, control engineering media technology and biomedical engineering. The results showed that the developed ULE, the EXOTIC, had a high level of usability, safety and adoptability. Further, the results showed that several topics are important to explicitly address in relation to the facilitation of interdisciplinary collaboration including, defining a common language, a joint visualization of the end goal and a physical frame for the collaboration, such as a shared laboratory. The study underlined the importance of interdisciplinarity and we believe that future collaboration amongst interdisciplinary researchers and centres, also at an international level, can strongly facilitate the usefulness and adoption of assistive exoskeletons and similar technologies.

User Based Development and Test of the EXOTIC Exoskeleton: Empowering Individuals with Tetraplegia Using a Compact, Versatile, 5-DoF Upper Limb Exoskeleton Controlled through Intelligent Semi-Automated Shared Tongue Control.

This paper presents the EXOTIC- a novel assistive upper limb exoskeleton for individuals with complete functional tetraplegia that provides an unprecedented level of versatility and control. The current literature on exoskeletons mainly focuses on the basic technical aspects of exoskeleton design and control while the context in which these exoskeletons should function is less or not prioritized even though it poses important technical requirements. We considered all sources of design requirements, from the basic technical functions to the real-world practical application. The EXOTIC features: (1) a compact, safe, wheelchair-mountable, easy to don and doff exoskeleton capable of facilitating multiple highly desired activities of daily living for individuals with tetraplegia; (2) a semi-automated computer vision guidance system that can be enabled by the user when relevant; (3) a tongue control interface allowing for full, volitional, and continuous control over all possible motions of the exoskeleton. The EXOTIC was tested on ten able-bodied individuals and three users with tetraplegia caused by spinal cord injury. During the tests the EXOTIC succeeded in fully assisting tasks such as drinking and picking up snacks, even for users with complete functional tetraplegia and the need for a ventilator. The users confirmed the usability of the EXOTIC.

Eyes-Free Tongue Gesture and Tongue Joystick Control of a Five DOF Upper-Limb Exoskeleton for Severely Disabled Individuals.

Spinal cord injury can leave the affected individual severely disabled with a low level of independence and quality of life. Assistive upper-limb exoskeletons are one of the solutions that can enable an individual with tetraplegia (paralysis in both arms and legs) to perform simple activities of daily living by mobilizing the arm. Providing an efficient user interface that can provide full continuous control of such a device-safely and intuitively-with multiple degrees of freedom (DOFs) still remains a challenge. In this study, a control interface for an assistive upper-limb exoskeleton with five DOFs based on an intraoral tongue-computer interface (ITCI) for individuals with tetraplegia was proposed. Furthermore, we evaluated eyes-free use of the ITCI for the first time and compared two tongue-operated control methods, one based on tongue gestures and the other based on dynamic virtual buttons and a joystick-like control. Ten able-bodied participants tongue controlled the exoskeleton for a drinking task with and without visual feedback on a screen in three experimental sessions. As a baseline, the participants performed the drinking task with a standard gamepad. The results showed that it was possible to control the exoskeleton with the tongue even without visual feedback and to perform the drinking task at 65.1% of the speed of the gamepad. In a clinical case study, an individual with tetraplegia further succeeded to fully control the exoskeleton and perform the drinking task only 5.6% slower than the able-bodied group. This study demonstrated the first single-modal control interface that can enable individuals with complete tetraplegia to fully and continuously control a five-DOF upper limb exoskeleton and perform a drinking task after only 2 h of training. The interface was used both with and without visual feedback.

OptimalTTF-1: Enhancing tumor treating fields therapy with skull remodeling surgery. A clinical phase I trial in adult recurrent glioblastoma.

BACKGROUND: Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the dose of tumor treating fields (TTFields) in glioblastoma (GBM) and prevents wasteful current shunting through the skin. SR-surgery introduces minor skull defects to focus the cancer-inhibiting currents toward the tumor and increase the treatment dose. This study aimed to test the safety and feasibility of this concept in a phase I setting. METHODS: Fifteen adult patients with the first recurrence of GBM were treated with personalized SR-surgery, TTFields, and physician's choice oncological therapy. The primary endpoint was toxicity and secondary endpoints included standard efficacy outcomes. RESULTS: SR-surgery resulted in a mean skull defect area of 10.6 cm2 producing a median TTFields enhancement of 32% (range 25-59%). The median TTFields treatment duration was 6.8 months and the median compliance rate 90%. Patients received either bevacizumab, bevacizumab/irinotecan, or temozolomide rechallenge. We observed 71 adverse events (AEs) of grades 1 (52%), 2 (35%), and 3 (13%). There were no grade 4 or 5 AEs or intervention-related serious AEs. Six patients experienced minor TTFields-induced skin rash. The median progression-free survival (PFS) was 4.6 months and the PFS rate at 6 months was 36%. The median overall survival (OS) was 15.5 months and the OS rate at 12 months was 55%. CONCLUSIONS: TTFields therapy combined with SR-surgery and medical oncological treatment is safe and nontoxic and holds the potential to improve the outcome for GBM patients through focal dose enhancement in the tumor.

[Tumor treating fields in cancer treatment in Denmark].

Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields is low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.

[Tumor treating fields in cancer treatment in Denmark].

Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields are low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.

Brain state-dependent stimulation boosts functional recovery following stroke.

OBJECTIVE: Adjuvant protocols devised to enhance motor recovery in subacute stroke patients have failed to show benefits with respect to classic therapeutic interventions. Here, we evaluate the efficacy of a novel brain state-dependent intervention based on known mechanisms of memory and learning that is integrated as part of the weekly rehabilitation program in subacute stroke patients. METHODS: Twenty-four hospitalized subacute stroke patients were randomly assigned to 2 intervention groups: (1) the associative group received 30 pairings of a peripheral electrical nerve stimulus (ES) such that the generated afferent volley arrived precisely during the most active phase of the motor cortex as patients attempted to perform a movement; and (2) in the control group, the ES intensity was too low to generate a stimulation of the nerve. Functional (including the lower extremity Fugl-Meyer assessment [LE-FM; primary outcome measure]) and neurophysiological (changes in motor evoked potentials [MEPs]) assessments were performed prior to and following the intervention period. RESULTS: The associative group significantly improved functional recovery with respect to the control group (median [interquartile range] LE-FM improvement = 6.5 [3.5-8.25] and 3 [0.75-3], respectively; p = 0.029). Significant increases in MEP amplitude were seen following all sessions in the associative group only (p ≤ 0.006). INTERPRETATION: This is the first evidence of a clinical effect of a neuromodulatory intervention in the subacute phase of stroke. This was evident with relatively few repetitions in comparison to available techniques, making it a clinically viable approach. The results indicate the potential of the proposed neuromodulation system in daily clinical routine for stroke rehabilitation. ANN NEUROL 2019;85:84-95.

Transcranial Direct Current Stimulation Potentiates Improvements in Functional Ability in Patients With Chronic Stroke Receiving Constraint-Induced Movement Therapy.

BACKGROUND AND PURPOSE: Transcranial direct current stimulation may enhance effect of rehabilitation in patients with chronic stroke. The objective was to evaluate the efficacy of anodal transcranial direct current stimulation combined with constraint-induced movement therapy of the paretic upper limb. METHODS: A total of 44 patients with stroke were randomly allocated to receive 2 weeks of constraint-induced movement therapy with either anodal or sham transcranial direct current stimulation. The primary outcome measure, Wolf Motor Function Test, was assessed at baseline and after the intervention by blinded investigators. RESULTS: Both groups improved significantly on all Wolf Motor Function Test scores. Group comparison showed improvement on Wolf Motor Function Test in the anodal group compared with the sham group. CONCLUSIONS: Anodal transcranial direct current stimulation combined with constraint-induced movement therapy resulted in improvement of functional ability of the paretic upper limb compared with constraint-induced movement therapy alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01983319.