The Berlin Bimanual Test for Tetraplegia (BeBiTT): development, psychometric properties, and sensitivity to change in assistive hand exoskeleton application.

BACKGROUND: Assistive hand exoskeletons are promising tools to restore hand function after cervical spinal cord injury (SCI) but assessing their specific impact on bimanual hand and arm function is limited due to lack of reliable and valid clinical tests. Here, we introduce the Berlin Bimanual Test for Tetraplegia (BeBiTT) and demonstrate its psychometric properties and sensitivity to assistive hand exoskeleton-related improvements in bimanual task performance. METHODS: Fourteen study participants with subacute cervical SCI performed the BeBiTT unassisted (baseline). Thereafter, participants repeated the BeBiTT while wearing a brain/neural hand exoskeleton (B/NHE) (intervention). Online control of the B/NHE was established via a hybrid sensorimotor rhythm-based brain-computer interface (BCI) translating electroencephalographic (EEG) and electrooculographic (EOG) signals into open/close commands. For reliability assessment, BeBiTT scores were obtained by four independent observers. Besides internal consistency analysis, construct validity was assessed by correlating baseline BeBiTT scores with the Spinal Cord Independence Measure III (SCIM III) and Quadriplegia Index of Function (QIF). Sensitivity to differences in bimanual task performance was assessed with a bootstrapped paired t-test. RESULTS: The BeBiTT showed excellent interrater reliability (intraclass correlation coefficients > 0.9) and internal consistency (α = 0.91). Validity of the BeBiTT was evidenced by strong correlations between BeBiTT scores and SCIM III as well as QIF. Wearing a B/NHE (intervention) improved the BeBiTT score significantly (p < 0.05) with high effect size (d = 1.063), documenting high sensitivity to intervention-related differences in bimanual task performance. CONCLUSION: The BeBiTT is a reliable and valid test for evaluating bimanual task performance in persons with tetraplegia, suitable to assess the impact of assistive hand exoskeletons on bimanual function.

Brain-Computer Interface-Controlled Exoskeletons in Clinical Neurorehabilitation: Ready or Not?

The development of brain-computer interface-controlled exoskeletons promises new treatment strategies for neurorehabilitation after stroke or spinal cord injury. By converting brain/neural activity into control signals of wearable actuators, brain/neural exoskeletons (B/NEs) enable the execution of movements despite impaired motor function. Beyond the use as assistive devices, it was shown that-upon repeated use over several weeks-B/NEs can trigger motor recovery, even in chronic paralysis. Recent development of lightweight robotic actuators, comfortable and portable real-world brain recordings, as well as reliable brain/neural control strategies have paved the way for B/NEs to enter clinical care. Although B/NEs are now technically ready for broader clinical use, their promotion will critically depend on early adopters, for example, research-oriented physiotherapists or clinicians who are open for innovation. Data collected by early adopters will further elucidate the underlying mechanisms of B/NE-triggered motor recovery and play a key role in increasing efficacy of personalized treatment strategies. Moreover, early adopters will provide indispensable feedback to the manufacturers necessary to further improve robustness, applicability, and adoption of B/NEs into existing therapy plans.

Depression and Emotions: When the Issues Expand the Horizons.

The COVID-19 pandemic has created several problems with uncertainties and fears that have intensified over time, with a subsequent explosion. The requests were diversified, but all focused on the "sense of containment" resulting from the increase in fear and uncertainty. The work carried out has had a change in structure and depth, as the majority of professionals in the psychological sector have had to change their assessment of perspective and approach in the work. It was no longer possible to have face-to-face sessions. This "upheaval" was perceived in a very tiring way with subsequent even serious side effects, initially associated with a change in the therapeutic alliance, with great effort in recovery and "mending". Many have amplified their psychosomatic problems with damage that can be recovered over time.

Post-stroke Rehabilitation of Severe Upper Limb Paresis in Germany - Toward Long-Term Treatment With Brain-Computer Interfaces.

Severe upper limb paresis can represent an immense burden for stroke survivors. Given the rising prevalence of stroke, restoration of severe upper limb motor impairment remains a major challenge for rehabilitation medicine because effective treatment strategies are lacking. Commonly applied interventions in Germany, such as mirror therapy and impairment-oriented training, are limited in efficacy, demanding for new strategies to be found. By translating brain signals into control commands of external devices, brain-computer interfaces (BCIs) and brain-machine interfaces (BMIs) represent promising, neurotechnology-based alternatives for stroke patients with highly restricted arm and hand function. In this mini-review, we outline perspectives on how BCI-based therapy can be integrated into the different stages of neurorehabilitation in Germany to meet a long-term treatment approach: We found that it is most appropriate to start therapy with BCI-based neurofeedback immediately after early rehabilitation. BCI-driven functional electrical stimulation (FES) and BMI robotic therapy are well suited for subsequent post hospital curative treatment in the subacute stage. BCI-based hand exoskeleton training can be continued within outpatient occupational therapy to further improve hand function and address motivational issues in chronic stroke patients. Once the rehabilitation potential is exhausted, BCI technology can be used to drive assistive devices to compensate for impaired function. However, there are several challenges yet to overcome before such long-term treatment strategies can be implemented within broad clinical application: 1. developing reliable BCI systems with better usability; 2. conducting more research to improve BCI training paradigms and 3. establishing reliable methods to identify suitable patients.

Heart rate variability predicts decline in sensorimotor rhythm control.

Objective.Voluntary control of sensorimotor rhythms (SMRs, 8-12 Hz) can be used for brain-computer interface (BCI)-based operation of an assistive hand exoskeleton, e.g. in finger paralysis after stroke. To gain SMR control, stroke survivors are usually instructed to engage in motor imagery (MI) or to attempt moving the paralyzed fingers resulting in task- or event-related desynchronization (ERD) of SMR (SMR-ERD). However, as these tasks are cognitively demanding, especially for stroke survivors suffering from cognitive impairments, BCI control performance can deteriorate considerably over time. Therefore, it would be important to identify biomarkers that predict decline in BCI control performance within an ongoing session in order to optimize the man-machine interaction scheme.Approach.Here we determine the link between BCI control performance over time and heart rate variability (HRV). Specifically, we investigated whether HRV can be used as a biomarker to predict decline of SMR-ERD control across 17 healthy participants using Granger causality. SMR-ERD was visually displayed on a screen. Participants were instructed to engage in MI-based SMR-ERD control over two consecutive runs of 8.5 min each. During the 2nd run, task difficulty was gradually increased.Main results.While control performance (p= .18) and HRV (p= .16) remained unchanged across participants during the 1st run, during the 2nd run, both measures declined over time at high correlation (performance: -0.61%/10 s,p= 0; HRV: -0.007 ms/10 s,p< .001). We found that HRV exhibited predictive characteristics with regard to within-session BCI control performance on an individual participant level (p< .001).Significance.These results suggest that HRV can predict decline in BCI performance paving the way for adaptive BCI control paradigms, e.g. to individualize and optimize assistive BCI systems in stroke.

Adaptation Strategies for Personalized Gait Neuroprosthetics.

Personalization of gait neuroprosthetics is paramount to ensure their efficacy for users, who experience severe limitations in mobility without an assistive device. Our goal is to develop assistive devices that collaborate with and are tailored to their users, while allowing them to use as much of their existing capabilities as possible. Currently, personalization of devices is challenging, and technological advances are required to achieve this goal. Therefore, this paper presents an overview of challenges and research directions regarding an interface with the peripheral nervous system, an interface with the central nervous system, and the requirements of interface computing architectures. The interface should be modular and adaptable, such that it can provide assistance where it is needed. Novel data processing technology should be developed to allow for real-time processing while accounting for signal variations in the human. Personalized biomechanical models and simulation techniques should be developed to predict assisted walking motions and interactions between the user and the device. Furthermore, the advantages of interfacing with both the brain and the spinal cord or the periphery should be further explored. Technological advances of interface computing architecture should focus on learning on the chip to achieve further personalization. Furthermore, energy consumption should be low to allow for longer use of the neuroprosthesis. In-memory processing combined with resistive random access memory is a promising technology for both. This paper discusses the aforementioned aspects to highlight new directions for future research in gait neuroprosthetics.

High Frequency Electrotherapy for the Treatment of Meibomian Gland Dysfunction.

PURPOSE: To test the safety and efficacy of high frequency electrotherapy (ET) on the clinical signs and symptoms of patients affected by dry eye and meibomian gland dysfunction (MGD). METHODS: Twenty-five patients affected by MGD were enrolled. Quantum Molecular Resonance ET was administered by means of the Rexon-Eye device 4 times, once per week for 4 weeks. Patients were reexamined 1 month after the last treatment. The primary endpoint was reduction in corneal fluorescein staining. Additional endpoints were tear break-up time, Ocular Surface Disease Index score, meibomian gland secretion score, and the number of expressible meibomian glands. Safety endpoints were Logarithm of the Minimum Angle of Resolution (LogMar) best spectacle-corrected visual acuity and intraocular pressure. RESULTS: Corneal fluorescein staining improved by 62.5% (P < 0.0001), tear breakup time increased by 30.9% (P < 0.0001), and the Ocular Surface Disease Index score improved by 37% (P < 0.001). The meibum quality and the number of expressible meibomian glands also increased (35.7% and 12%, P < 0.001 and P < 0.0001, respectively). Schirmer test scores increased after treatment by 16.5% (P = 0.01). No adverse events were observed. CONCLUSIONS: Quantum Molecular Resonance ET appears to be safe and significantly reduces symptoms and signs associated with MGD. It may have a relevant role in the treatment of evaporative dry eye disease.

The Role of the Social Networks, between a Utility and a New Addiction.

The reality of social networks in recent years has taken on new and enriching scenarios, to learn more about the problems and complex dynamics of life that surround the generations of preadolescents and adolescents. This work has matured over several years, interacting with schools in the Campania region (southern Italy), meeting and talking with teachers, parents and students, observing the reality that surrounds them. The territory of Naples and its province was the one in which the activity was mainly carried out. It has been found that the new frontiers of youth language find their maximum form of exposure in sharing, exhibition, media "exposure", through the channel of the narration of their daily life "live" (most of the time), often it implies a high probability of incurring dangers and dangers that are difficult to manage, as "children" of an age in which to exhibit is in conformity with the historical moment. The definition given by the experts is "Digital Natives", "Digital Immigrants" are adults, who have a different and less fluid approach compared to the reality of youth. Dangers, pitfalls and others are amplified through the simple sharing of one's own experiences. This work benefited from the help of various professional figures, which made sure that some difficult aspects and contexts could emerge. Some problems of this reality linked to social networks are distinguished in a more specific and authentic way.

The social networks: new challenge or new addiction?

The reality of Social networks provides a fascinating and enhancing opportunity to understand the issues and life dynamics of generations of pre-adolescents and adolescents; This study has matured over three years of work in the schools of Campania (southern Italy), observing all the provinces, with a predominance of those of the Neapolitan territory. It has been found that the language of the boys finds its maximal expression in using social media to share, exhibit, and tell their experience of living every day their daily lives, with a high probability of encountering very interesting pitfalls and dangers... because they are "children" of a period when to exhibit themselves is in accordance with current fashion. These dangers and pitfalls are amplified by simply sharing, and sharing this work with professionals has helped to better monitor some contexts and difficulties which have emerged with difficulty and have helped to shed light on more specific and authentic issues regarding this reality.

Preliminary results of contrast-enhanced sonography in the evaluation of the response of uveal melanoma to gamma-knife radiosurgery.

PURPOSE: Our aim was to prospectively analyze the use of contrast-enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma-knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR. METHODS: Ten patients with UM treated with GKR underwent sonography (US) and CEUS at baseline and at 3, 6, and 12 months after GKR. The transverse diameter, thickness, and quantitative parameters of the UM (ie, area under the curve in the wash-in phase, wash-in perfusion index, peak enhancement, and wash-in rate) were calculated by using dedicated software and compared by using Wilcoxon's signed-rank test. RESULTS: The mean tumor thickness on US was significantly less at both 6 (6.6 mm) and 12 months after GKR (5.8 mm) than it was at baseline (8.3 mm; p < 0.05, both comparisons). Compared with baseline data, the median flow quantitative parameters on CEUS were significantly changed as follows: the peak enhancement (in arbitrary units [au]) at baseline was 5 × 10(6) ; 6 months after GKR, it was 2 × 10(1) (p < 0.05), and 12 months after GKR, it was 4 × 10(1) (p < 0.05). The wash-in rate (in au) at baseline was 1 × 10(6) ; 6 months after GKR, it was 2.1 (p < 0.05), and 12 months after GKR, it was 9.3 (p < 0.05). The wash-in perfusion index (in au) at baseline was 2 × 10(7) ; 6 months after GKR, it was 7 × 10(1) (p < 0.05), and 12 months after GKR, it was 1 × 10(2) (p < 0.05). The area under the curve during the wash-in phase (in au) at baseline was 1 × 10(8) ; 12 months after GKR, it was reduced to 6 × 10(2) (p < 0.05). CONCLUSIONS: At 6 months after GKR, a reduction of tumor thickness, as detected on US, occurred in 6 of the 10 patients, whereas a reduction in all the quantitative parameters measured on CEUS occurred in all 10 patients. However, a larger population is needed to investigate whether CEUS could become the first-choice technique for monitoring the response of UM to GKR.

Birdshot retinochoroidopathy masquerading as intraocular lymphoma.

We present a case of a patient with bilateral posterior uveitis HLA-A29 positive, masquerading intraocular lymphoma. A 43 year-old woman presented with bilateral vitritis and chorioretinal lesions compatible with "birdshot lesions". The patient was initially diagnosed with birdshot retinochoroidopathy and later on, during follow up, the occurrence of neurologic involvement and the lack of response to systemic immunosuppression led us to re-evaluate the diagnosis. A definite diagnosis of intraocular lymphoma with central nervous system involvement was made. This case is presented to highlight the importance of careful follow-up of patients with chronic uveitis and re-evaluation of systemic symptoms and signs, in particular when ocular findings are highly suggestive for masquerade syndrome.

Ex vivo enrichment of circulating anti-tumor T cells from both cutaneous and ocular melanoma patients: clinical implications for adoptive cell transfer therapy.

Tumor-infiltrating lymphocytes (TILs) have been successfully used for adoptive cell transfer (ACT) immunotherapy; however, due to their scarce availability, this therapy is possible for a limited fraction of cutaneous melanoma patients. We assessed whether an effective protocol for ex vivo T-cell expansion from peripheral blood mononuclear cells (PBMCs), suitable for ACT of both cutaneous and ocular melanoma patients, could be identified. PBMCs from both cutaneous and ocular melanoma patients were stimulated in vitro with autologous, irradiated melanoma cells (mixed lymphocyte tumor cell culture; MLTCs) in the presence of IL-2 and IL-15 followed by the rapid expansion protocol (REP). The functional activity of these T lymphocytes was characterized and compared with that of TILs. In addition, the immune infiltration in vivo of ocular melanoma lesions was analyzed. An efficient in vitro MLTC expansion of melanoma reactive T cells was achieved from all PBMC's samples obtained in 7 cutaneous and ocular metastatic melanoma patients. Large numbers of melanoma-specific T cells could be obtained when the REP protocol was applied to these MLTCs. Most MLTCs were enriched in non-terminally differentiated T(EM) cells homogeneously expressing co-stimulatory molecules (e.g., NKG2D, CD28, CD134, CD137). A similar pattern of anti-tumor activity, in association with a more variable expression of co-stimulatory molecules, was detected on short-term in vitro cultured TILs isolated from the same patients. In these ocular melanoma patients, we observed an immune infiltrate with suppressive characteristics and a low rate of ex vivo growing TILs (28.5% of our cases). Our MLTC protocol overcomes this limitation, allowing the isolation of T lymphocytes with effector functions even in these patients. Thus, anti-tumor circulating PBMC-derived T cells could be efficiently isolated from melanoma patients by our novel ex vivo enrichment protocol. This protocol appears suitable for ACT studies of cutaneous and ocular melanoma patients.

Serous Retinal Detachments Complicating Interferon-α and Ribavirin Treatment in Patients with Hepatitis C.

PURPOSE: To report the cases of two patients with chronic hepatitis C infection showing serous retinal detachments similar to Vogt-Koyanagi-Harada (VKH) disease. METHODS: We reviewed the clinical records of two patients who were diagnosed with VKH-like disease during combined interferon-α (IFNα) and ribavirin treatment. RESULTS: Interruption of IFNα and ribavirin treatment in association with oral corticosteroids resulted in a favorable visual outcome in the case of diffuse retinal detachment (case 1). On the contrary, visual acuity did not improve when late cicatricial stage disease was already present (case 2). CONCLUSIONS: There is increasing evidence of a link between hepatitis C virus infection treated with pegylated IFNα-2b and the development of VKH-like disease. Knowing the potential side effects of IFNα and ribavirin administration is fundamentally important, as is the need to closely follow up those patients that need to undergo this treatment.

Intralesional rituximab: a new therapeutic approach for patients with conjunctival lymphomas.

OBJECTIVE: The tolerability and activity of the intralesional administration of rituximab, a chimeric monoclonal antibody that targets the CD20 antigen, was assessed in patients with conjunctival B-cell lymphoma. The systemic administration of rituximab has varying response rates with different types of lymphoma, generally with a mild toxicity level. Intralesional administration of this drug has increased local disease control in cases of cutaneous mucosa-associated lymphoid tissue (MALT) lymphoma. DESIGN: This was an interventional pilot study of 3 patients with relapsed CD20+ conjunctival lymphomas treated with intralesional injections of rituximab. PARTICIPANTS: Two patients with conjunctival MALT lymphoma refractory to previous systemic treatment with rituximab and 1 patient with relapsed follicular lymphoma of the eyelid were included in the study. METHODS: Patients received 4 weekly intralesional injections followed by 6 monthly injections of undiluted rituximab together with xylocaine 2%. MAIN OUTCOME MEASURES: Side effects and tumor response were assessed before each intralesional injection and at 3-month intervals after treatment conclusion. RESULTS: The 2 conjunctival MALT lymphoma patients achieved complete remission after intraconjunctival rituximab treatment, which shows that this method of administration can overcome the primary resistance to this monoclonal antibody. The patient with the eyelid follicular lymphoma did not achieve tumor regression after the first intralesional injections of rituximab. In this patient, the addition of autologous serum resulted in lymphoma remission at the end of treatment, suggesting that drug inefficacy can be related to the low bioavailability of effectors in the tumor tissue. CONCLUSIONS: Although follow-up is still short, these preliminary findings suggest that intralesional rituximab is a well-tolerated strategy in marginal-zone and follicular lymphomas of the conjunctiva. An increased bioavailability of effectors in the tumor tissue, by means of the addition of autologous serum, may improve rituximab activity. This strategy could be used in other extranodal CD20+ indolent lymphomas to improve local control, even in patients who are initially refractory to systemic rituximab treatment.

Quality of life in patients with uveitis on chronic systemic immunosuppressive treatment.

OBJECTIVE: To assess health-related quality of life with Italian SF-36 in patients with uveitis on chronic systemic immunosuppressants. METHODS: Consecutive patients with chronic noninfectious uveitis on systemic immunosuppressive treatment seen at the Ocular Immunology Service, San Raffaele Scientific Institute, Milan, were enrolled. Health status was evaluated with the Italian version of the SF-36 questionnaire in 8 dimensions: physical functioning, physical disability, body pain, general health, vitality, social functioning, emotional disability, mental health. Statistical analysis of variance was used to test for differences in SF-36 scores between subgroups of interest (age, sex, educational level, location and laterality of uveitis, systemic associated diseases, visual acuity, systemic treatment, duration of disease). RESULTS: One hundred Caucasian patients (35 female, 65 male) with a median age of 46.31 years (range 10-76) were examined. Uveitis was bilateral in 88% of patients. Uveitis location was anterior (12%), intermediate (10%), posterior (34%), and panuveitis (44%). The most frequent diagnoses were idiopathic (32%), sarcoidosis (15%), and Behçet disease (15%). The SF-36 physical and mental component summary scores were lower among uveitis patients than those of the general Italian population; the most statistically significant differences found in subgroups were older age, female sex, low visual acuity (<20/40), and long-standing duration of the disease (>6 years). CONCLUSIONS: Italian patients with uveitis on chronic systemic immunosuppressants reported markedly poorer general health status than normal matched population subjects. The quality of life of these patients seems to be significantly related to visual acuity and disease duration.

Anterior uveitis complicating zoledronic acid infusion.

Zoledronic acid is the most effective treatment in patients with hypercalcemia secondary to malignancy; occasionally it can be related to ocular inflammation. We report a case of severe unilateral anterior uveitis following administration of intravenous zoledronic acid in a patient with frontal hyperostosis secondary to breast cancer. The patient developed anterior uveitis 24 hours after the administration of intravenous zoledronate. The patient was treated with topical prednisone and cycloplegic eye drops, with complete recovery after one month. This report shows that, on rare occasions, zoledronic acid can be a possible cause of acute anterior uveitis.