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Importance Many patients with generalized myasthenia gravis (gMG) have substantial clinical disability, persistent disease burden, and adverse effects attributable to chronic immunosuppression. Therefore, there is a significant need for targeted, well-tolerated therapies with the potential to improve disease control and enhance quality of life. Objective To evaluate the clinical effects of zilucoplan, a subcutaneously (SC) self-administered macrocyclic peptide inhibitor of complement component 5, in a broad population of patients with moderate to severe gMG. Design, Setting, and Participants This randomized, double-blind, placebo-controlled phase 2 clinical trial at 25 study sites across North America recruited participants between December 2017 and August 2018. Fifty-seven patients were screened, of whom 12 did not meet inclusion criteria and 1 was lost to follow-up after randomization but before receiving study drug, resulting in a total of 44 acetylcholine receptor autoantibody (AChR-Ab)–positive patients with gMG with baseline Quantitative Myasthenia Gravis (QMG) scores of at least 12, regardless of treatment history. Interventions Patients were randomized 1:1:1 to a daily SC self-injection of placebo, 0.1-mg/kg zilucoplan, or 0.3-mg/kg zilucoplan for 12 weeks. Main Outcomes and Measures The primary and key secondary end points were the change from baseline to week 12 in QMG and MG Activities of Daily Living scores, respectively. Significance testing was prespecified at a 1-sided α of .10. Safety and tolerability were also assessed. Results The study of 44 patients was well balanced across the 3 treatment arms with respect to key demographic and disease-specific variables. The mean age of patients across all 3 treatment groups ranged from 45.5 to 54.6 years and most patients were white (average proportions across 3 treatment groups: 78.6%-86.7%). Clinically meaningful and statistically significant improvements in primary and key secondary efficacy end points were observed. Zilucoplan at a dose of 0.3 mg/kg SC daily resulted in a mean reduction from baseline of 6.0 points in the QMG score (placebo-corrected change, –2.8;P = .05) and 3.4 points in the MG Activities of Daily Living score (placebo-corrected change, –2.3;P = .04). Clinically meaningful and statistically significant improvements were also observed in other secondary end points, the MG Composite and MG Quality-of-Life scores. Outcomes for the 0.1-mg/kg SC daily dose were also statistically significant but slower in onset and less pronounced than with the 0.3-mg/kg dose. Rescue therapy (intravenous immunoglobulin or plasma exchange) was required in 3 of 15, 1 of 15, and 0 of 14 participants in the placebo, 0.1-mg/kg zilucoplan, and 0.3-mg/kg zilucoplan arms, respectively. Zilucoplan was observed to have a favorable safety and tolerability profile. Conclusions and Relevance Zilucoplan yielded rapid, meaningful, and sustained improvements over 12 weeks in a broad population of patients with moderate to severe AChR-Ab–positive gMG. Near-complete complement inhibition appeared superior to submaximal inhibition. The observed safety and tolerability profile of zilucoplan was favorable. Trial Registration ClinicalTrials.gov Identifier:NCT03315130.

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Objectives/Hypothesis Vocal fold motion asymmetry (VFMA) is often attributed to vocal fold paresis or an anatomical variant. Although laryngeal electromyography (LEMG) may be used to evaluate patients with vocal fold paresis, electrodiagnostic findings in VFMA have not been well defined. Study Design Review of a case series Methods Twenty-five symptomatic patients with VFMA were examined by LEMG, and the findings were analyzed. Results Although all were thought to have unilateral recurrent laryngeal nerve paresis, LEMG showed only nine to have unilateral recurrent nerve paresis. There were nine with both ipsilateral recurrent laryngeal nerve and superior laryngeal nerve paresis, four with bilateral paresis, and three were normal. Reduced total number of units, reduced recruitment, motor units firing fast, and polyphasic units were more common, whereas fibrillation potentials, fasciculation, positive sharp waves, and complex repetitive discharges were uncommon. The LEMG findings are most consistent with old, healed neuropathy. McNemar's test for the acute versus chronic denervation potentials showed significant differences. Conclusions VFMA has a high incidence of vocal fold paresis that can be better defined by LEMG. The site and side of paresis is often wrong based on laryngoscopy findings alone. The LEMG findings of VFMA appear to be consistent with old, healed neuropathy Level of Evidence 4 Laryngoscope, 2016

The efficacy of thymectomy and the optimal surgical technique in the treatment of myasthenia gravis (MG) remain controversial. Long-term outcomes are lacking and remission rates are based on small populations. We reviewed our institutional experience of thymectomy for MG focusing on long-term outcomes, complete stable remission (CSR), improvement of symptoms, after transcervical, transsternal, thoracotomy, and VATS thymectomy. A retrospective review of a prospectively maintained database of 3017 patients from 1941-2013 with MG was performed. Patients who underwent thymectomy with follow-up data including age at the time of surgery, sex, date of onset of symptoms, date of surgery, Osserman classification before and after surgery, surgical technique, date of remission, and status at last follow-up were included in the analysis. CSR and prognostic factors were analyzed by crude rate, Kaplan-Meier estimate, chi-squared test, Wilcoxon test, and a Cox proportional model. Overall, 1002 thymectomy patients with complete data were analyzed, and 35.5% (n = 355) derived benefit from surgery. Crude rate CSR was 19% (n = 191) and an additional 16% (n = 164) symptomatically improved requiring less medication after thymectomy. Also, 58% (n = 580) were stable after resection, and 6.7% (n = 67) developed progressive disease. Kaplan-Meier estimates of CSR were 27.7%, 36.7%, and 47.3% at 10, 25, and 40 years, respectively. On multivariate analysis, transsternal technique, thymoma, and preoperative Osserman classification were significantly associated with failure to achieve CSR. Thymectomy provides long-term CSR in 47.3% of patients with long-term follow-up. Patients with MG should be offered thymectomy when possible.

Objectives/Hypothesis The diagnosis of paresis in patients with vocal fold motion impairment remains a challenge. More than 27 clinical parameters have been cited that may signify paresis. We hypothesize that some features are more significant than others. Study Design Prospective case series. Methods Two laryngologists rated laryngoscopy findings in 19 patients suspected of paresis. The diagnosis was confirmed with laryngeal electromyography. A standard set of 27 ratings was used for each examination that included movement, laryngeal configuration, and stroboscopy signs. A Fisher exact test was completed for each measure. A kappa coefficient was calculated for effectiveness in predicting the laterality of paresis. Results Left-sided vocal fold paresis (n = 13) was significantly associated with ipsilateral axis deviation, thinner vocal fold, bowing, reduced movement, reduced kinesis, and phase lag (P < .05). Right-sided vocal fold paresis (n = 6) was significantly associated with ipsilateral shorter vocal fold, axis deviation, reduced movement, and reduced kinesis (P < .05). Using these key parameters, the senior author was accurately able to diagnose the side of paresis in 89.5% of cases for a kappa coefficient of 0.78. Conclusions Of the multiple features on laryngoscopy, glottic configuration, ipsilateral thin vocal fold, vocal fold bowing, reduced movement, reduced kinesis, and phase lag were more likely to be associated with vocal fold paresis. Level of Evidence 4 Laryngoscope, 2015

A virtual reality (VR) augmented cycling kit (VRACK) was developed to address motor control and fitness deficits of individuals with chronic stroke. In this article, we report on the safety, feasibility, and efficacy of using the VR augmented cycling kit to improve cardiorespiratory (CR) fitness of individuals in the chronic phase poststroke.Four individuals with chronic stroke (47-65 years old and ≥3 years poststroke), with residual lower extremity impairments (Fugl-Meyer 24-26/34), who were limited community ambulators (gait speed range 0.56-1.1 m/s) participated in this study. Safety was defined as the absence of adverse events. Feasibility was measured using attendance, total exercise time, and "involvement" measured with the presence questionnaire (PQ). Efficacy of CR fitness was evaluated using a submaximal bicycle ergometer test before and after an 8-week training program.The intervention was safe and feasible with participants having 1 adverse event, 100% adherence, achieving between 90 and 125 minutes of cycling each week, and a mean PQ score of 39 (SD 3.3). There was a statistically significant (13%; P = 0.035) improvement in peak VO(2), with a range of 6% to 24.5%.For these individuals, poststroke, VR augmented cycling, using their heart rate to set their avatar's speed, fostered training of sufficient duration and intensity to promote CR fitness. In addition, there was a transfer of training from the bicycle to walking endurance. VR augmented cycling may be an addition to the therapist's tools for concurrent training of mobility and health promotion of individuals poststroke.

O neuronio motor caracteriza-se pela distribuicao n a regiao anterior da medula e tronco cerebral desempenhando papel de integracao de impulsos de origem do sistema nervoso central e a tividade muscular. Para e stabelecer determinada funcao, torna-se necessario u ma e strutura a primorada, d e a lta a tividade metabolica, constituida de um corpo celular, axonio extenso com ramificacoes dendriticas frequentes s ustentadas por um citoesqueleto e porcao terminal integrado a juncao neuromuscular e musculo esqueletico. O corpo celular apresenta alta a tividade oxidativa mitocondrial necessarias para a producao d e e nzimas e outras proteinas responsaveis pela manutencao da integridade funcional, eliminando residuos toxicos a celula, estruturando o citoesqueleto para garantia de um t ransporte a xonal adequado, garantindo a neuroprotecao d iante do stress metabolico. O axonio constitui-se de fibras grossas mielinizadas, d e rapida c onducao, transmitindo um impulso originado por input excitatorio glutamatergico. As patologias que a fetam o n euronio motor caracterizam-se por causarem apoptose neuronal, isto e dano na estrutura funcional celular, seja por alteracoes do DNA ou por stress funcional, ou necrose c om agressao d ireta a o n euronio motor como na poliomielite, alem disto, nota-se que as patologias diferem-se na variabilidade de acometimento anatomico, com seletividade por locais e organelas especificas, reforcando as varias possibilidades etiologicas. A doenca do neuronio motor e um t ermo q ue se a plica a sindromes clinicas com caracteristicas proprias como a Esclerose Lateral Amiotrofica (ELA), Atrofia Muscular Progressiva (AMP), Esclerose Lateral Primaria (ELP), Paralisia Bulbar Progressiva(PBP). A Esclerose Lateral Amiotrofica, caracteriza-se por uma doenca degenerativa, q ue afeta o corno anterior da medula, tronco cerebral e celulas de Betz do cortex motor, causando morte no corpo celular do neuronio motor de maneira cronica e rapidamente progressiva com obito em torno de 03 a 05 anos apos o inicio da sintomatologia .

Maselli RA, Arredondo J, Cagney O, Mozaffar T, Skinner S, Yousif S, Davis RR, Gregg JP, Sivak M, Konia TH, Thomas K, Wollmann RL. Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE. Mutations in the plectin gene (PLEC1) cause epidermolysis bullosa simplex (EBS), which may associate with muscular dystrophy (EBS–MD) or pyloric atresia (EBS–PA). The association of EBS with congenital myasthenic syndrome (CMS) is also suspected to result from PLEC1 mutations. We report here a consanguineous patient with EBS and CMS for whom mutational analysis of PLEC1 revealed a homozygous 36 nucleotide insertion (1506_1507ins36) that results in a reduced expression of PLEC1 mRNA and plectin in the patient muscle. In addition, mutational analysis of CHRNE revealed a homozygous 1293insG, which is a well-known low-expressor receptor mutation. A skin biopsy revealed signs of EBS, and an anconeus muscle biopsy showed signs of a mild myopathy. Endplate studies showed fragmentation of endplates, postsynaptic simplification, and large collections of thread-like mitochondria. Amplitudes of miniature endplate potentials were diminished, but the endplate quantal content was actually increased. The complex phenotype presented here results from mutations in two separate genes. While the skin manifestations are because of the PLEC1 mutation, footprints of mutations in PLEC1 and CHRNE are present at the neuromuscular junction of the patient indicating that abnormalities in both genes contribute to the CMS phenotype.

Progression of disease and effectiveness of therapy in patients with amyotrophic lateral sclerosis (ALS) are determined by both questionnaire- and examination-based measures. To determine whether both types of measurement tools are equally predictive at all stages of disease, we compared questionnaire-based ALS Functional Rating Scale (ALSFRS) scores to the examination-based Appel ALS (AALS) scores at different stages of disease. Same-day scores were obtained during 174 visits in 62 patients with definite or probable ALS. Using normalized scores, correlation between the scales and predictability were best in mildly affected patients. Predictions of ALSFRS based on AALS scores were less than half as precise in the later stages of disease. Both scales showed significant change with disease progression, but ALSFRS consistently underestimated disease severity defined by AALS (P < 0.001). Questionnaire-based measurements should be compared against objective scales at all stages of disease severity before they are accepted as primary endpoint measures.

The diagnosis of paresis in patients with vocal fold motion impairment remains a challenge. More than 27 clinical parameters have been cited that may signify paresis. We hypothesize that some features are more significant than others.Prospective case series.Two laryngologists rated laryngoscopy findings in 19 patients suspected of paresis. The diagnosis was confirmed with laryngeal electromyography. A standard set of 27 ratings was used for each examination that included movement, laryngeal configuration, and stroboscopy signs. A Fisher exact test was completed for each measure. A kappa coefficient was calculated for effectiveness in predicting the laterality of paresis.Left-sided vocal fold paresis (n = 13) was significantly associated with ipsilateral axis deviation, thinner vocal fold, bowing, reduced movement, reduced kinesis, and phase lag (P.05). Right-sided vocal fold paresis (n = 6) was significantly associated with ipsilateral shorter vocal fold, axis deviation, reduced movement, and reduced kinesis (P.05). Using these key parameters, the senior author was accurately able to diagnose the side of paresis in 89.5% of cases for a kappa coefficient of 0.78.Of the multiple features on laryngoscopy, glottic configuration, ipsilateral thin vocal fold, vocal fold bowing, reduced movement, reduced kinesis, and phase lag were more likely to be associated with vocal fold paresis.4 Laryngoscope, 126:1831-1836, 2016.

Summary Objective The diagnosis of paresis in patients with vocal fold motion impairment remains a challenge. In particular, laryngoscopy examination may result in significant disagreement in diagnosis among providers. We hypothesize that systematically evaluating for a standard set of clinical parameters will increase the diagnostic concordance among providers. Study design Prospective case series conducted at a Tertiary referral Laryngology office. Methods Two laryngologists (rater 1) and two trainees (rater 2) rated laryngoscopy findings in 19 patients suspected of paresis. The diagnosis was confirmed with laryngeal electromyogram. A standard set of 27 ratings was used for each examination that included movement, laryngeal configuration, and stroboscopy signs. A kappa coefficient was calculated for agreement in laryngoscopy findings and effectiveness in predicting the laterality of paresis. Results A substantial agreement (kappa coefficient > 0.61) existed between the raters for vocal fold length, vocal fold thickness, bowing, and reduction in movement. A moderate agreement (kappa coefficient > 0.41) existed between raters for piriform opening and reduced kinesis. The senior author was accurately able to diagnose the side of paresis in 89.5% of cases for a kappa coefficient of 0.78, whereas the trainees correctly predicted the side of paresis in 63.1% for a kappa coefficient of 0.35. The raters agreed on the diagnosis in 73.7% of cases for a kappa coefficient of 0.50. Conclusions Using a standard set of laryngoscopy findings may improve the provider's ability to identify the laterality of vocal fold paresis and increase interrater reliability compared with other series.

Vocal fold motion asymmetry (VFMA) is often attributed to vocal fold paresis or an anatomical variant. Although laryngeal electromyography (LEMG) may be used to evaluate patients with vocal fold paresis, electrodiagnostic findings in VFMA have not been well defined.Review of a case seriesTwenty-five symptomatic patients with VFMA were examined by LEMG, and the findings were analyzed.Although all were thought to have unilateral recurrent laryngeal nerve paresis, LEMG showed only nine to have unilateral recurrent nerve paresis. There were nine with both ipsilateral recurrent laryngeal nerve and superior laryngeal nerve paresis, four with bilateral paresis, and three were normal. Reduced total number of units, reduced recruitment, motor units firing fast, and polyphasic units were more common, whereas fibrillation potentials, fasciculation, positive sharp waves, and complex repetitive discharges were uncommon. The LEMG findings are most consistent with old, healed neuropathy. McNemar's test for the acute versus chronic denervation potentials showed significant differences.VFMA has a high incidence of vocal fold paresis that can be better defined by LEMG. The site and side of paresis is often wrong based on laryngoscopy findings alone. The LEMG findings of VFMA appear to be consistent with old, healed neuropathy4 Laryngoscope, 126:E273-E277, 2016.

We studied a patient with ophthalmoparesis and pupillary areflexia 2 weeks after a viral syndrome. Miller Fisher syndrome was suspected but GQ1b antibodies were not detected. To define neuromuscular involvement we performed electrodiagnostic studies. Single-fiber electromyography (SFEMG) in the extensor digitorum communis (EDC) showed abnormal jitter and axonal blocking, suggesting terminal axon dysfunction. Subsequent GQ1b antibody titers were elevated to borderline levels. Clinical symptoms gradually resolved. SFEMG may help characterize neuropathies associated with antibodies to neuronal ganglioside and identify involvement of the terminal axon and neuromuscular junction. Muscle Nerve 2006

Stroke is a leading cause of serious long-term disability in the United States. There is a need for new technological adjuncts to expedite patients' scheduled discharge from hospital and pursue rehabilitation procedure at home. SQUID is a low-cost, smart shirt that incorporates a six-channel electromyography (EMG) and heart rate data acquisition module to deliver objective audiovisual and haptic biofeedback to the patient. The sensorized shirt is interfaced with a smartphone application, for the subject's usage at home, as well as the online database, for the therapist's remote supervision from hospital. A single healthy subject was recruited to investigate the system functionality during improperly performed exercise. The system can potentially be used in automated, remote monitoring of variety of physical therapy exercises, rooted in strength or coordination training of specific muscle groups.

Background Cycling has been used in the rehabilitation of individuals with both chronic and post-surgical conditions. Among the challenges with implementing bicycling for rehabilitation is the recruitment of both extremities, in particular when one is weaker or less coordinated. Feedback embedded in virtual reality (VR) augmented cycling may serve to address the requirement for efficacious cycling; specifically recruitment of both extremities and exercising at a high intensity. Methods In this paper a mechatronic rehabilitation bicycling system with an interactive virtual environment, called Virtual Reality Augmented Cycling Kit (VRACK), is presented. Novel hardware components embedded with sensors were implemented on a stationary exercise bicycle to monitor physiological and biomechanical parameters of participants while immersing them in an augmented reality simulation providing the user with visual, auditory and haptic feedback. This modular and adaptable system attaches to commercially-available stationary bicycle systems and interfaces with a personal computer for simulation and data acquisition processes. The complete bicycle system includes: a) handle bars based on hydraulic pressure sensors; b) pedals that monitor pedal kinematics with an inertial measurement unit (IMU) and forces on the pedals while providing vibratory feedback; c) off the shelf electronics to monitor heart rate and d) customized software for rehabilitation. Bench testing for the handle and pedal systems is presented for calibration of the sensors detecting force and angle. Results The modular mechatronic kit for exercise bicycles was tested in bench testing and human tests. Bench tests performed on the sensorized handle bars and the instrumented pedals validated the measurement accuracy of these components. Rider tests with the VRACK system focused on the pedal system and successfully monitored kinetic and kinematic parameters of the rider’s lower extremities. Conclusions The VRACK system, a virtual reality mechatronic bicycle rehabilitation modular system was designed to convert most bicycles in virtual reality (VR) cycles. Preliminary testing of the augmented reality bicycle system was successful in demonstrating that a modular mechatronic kit can monitor and record kinetic and kinematic parameters of several riders.

Background Prefabricated orthotic devices are currently designed to fit a range of patients and therefore they do not provide individualized comfort and function. Custom-fit orthoses are superior to prefabricated orthotic devices from both of the above-mentioned standpoints. However, creating a custom-fit orthosis is a laborious and time-intensive manual process performed by skilled orthotists. Besides, adjustments made to both prefabricated and custom-fit orthoses are carried out in a qualitative manner. So both comfort and function can potentially suffer considerably. A computerized technique for fabricating patient-specific orthotic devices has the potential to provide excellent comfort and allow for changes in the standard design to meet the specific needs of each patient. Methods In this paper, 3D laser scanning is combined with rapid prototyping to create patient-specific orthoses. A novel process was engineered to utilize patient-specific surface data of the patient anatomy as a digital input, manipulate the surface data to an optimal form using Computer Aided Design (CAD) software, and then download the digital output from the CAD software to a rapid prototyping machine for fabrication. Results Two AFOs were rapidly prototyped to demonstrate the proposed process. Gait analysis data of a subject wearing the AFOs indicated that the rapid prototyped AFOs performed comparably to the prefabricated polypropylene design. Conclusions The rapidly prototyped orthoses fabricated in this study provided good fit of the subject's anatomy compared to a prefabricated AFO while delivering comparable function (i.e. mechanical effect on the biomechanics of gait). The rapid fabrication capability is of interest because it has potential for decreasing fabrication time and cost especially when a replacement of the orthosis is required.

Quality, amplitude and frequency of the interaction forces between a human and an actuator are essential traits for haptic applications. A variety of Electro-Active Polymer (EAP) based actuators can provide these characteristics simultaneously with quiet operation, low weight, high power density and fast response. This paper demonstrates a rolled Dielectric Elastomer Actuator (DEA) being used as a telepresence device in a heart beat measurement application. In the this testing, heart signals were acquired from a remote location using a wireless heart rate sensor, sent through a network and DEA was used to haptically reproduce the heart beats at the medical expert's location. A series of preliminary human subject tests were conducted that demonstrated that a) DE based haptic feeling can be used in heart beat measurement tests and b) through subjective testing the stiffness and actuator properties of the EAP can be tuned for a variety of applications.

A haptic system for hand rehabilitation is presented that combines robotics and interactive virtual reality to facilitate repetitive performance of task specific exercises for patients recovering from neurological motor deficits. A two degree of freedom robotic interface allows coordinated motions of the forearm and the hand (pronation/supination and grasp/release, respectively). It is driven by two novel Electro-Rheological Fluid (ERF) based hydraulic actuators. Tests were conducted to characterize these actuators, and feed-forward controllers were developed for their force/torque control. A virtual reality environment (maze game) was developed in which the robot applies force fields to the user as the user navigates the environment, forming a haptic interface between the patient and the game. Proof of concept testing was performed on the virtual environment to analyze the use interaction of haptic feedback and a virtual game.

In this paper the virtual reality augmented cycling kit (VRACK) a mechatronic rehabilitation system with an interactive virtual environment is presented. It was designed as a modular system that can convert most bicycles in virtual reality (VR) cycles. Novel hardware components embedded with sensors were implemented on a stationary exercise bicycle to monitor physiological and biomechanical parameters of participants while immersing them in a virtual reality simulation providing the user with visual, auditory and haptic feedback. This modular and adaptable system attaches to commercially-available stationary bicycle systems and interfaces with a personal computer for simulation and data acquisition processes. The bicycle system includes novel handle bars based on hydraulic pressure sensors and innovative pedals that monitor lower extremity kinetics and kinematics. Parameters monitored by these systems are communicated to a practitioner's interface screen and can be amplified before entering its virtual environment. The first prototype of the system was successful in demonstrating that a modular mechatronic kit can monitor and record kinetic, kinematic and physiologic parameters of riders.

The ability to control the ankle muscles and produce adequate range of motion in the ankle joints are key components of gait and balance function. Patients who suffer from neurological impairments, such as stroke or traumatic brain injury, frequently lose gait and balance function due in part to loss of ankle control. Described in this paper is a unique two degree of freedom (DOF) mechatronic device with a virtual reality interface that has been developed to meet the needs of such patients for ankle and balance rehabilitation. The Northeastern University Virtual Ankle and Balance Trainer (NUVABAT) rehabilitation system has five components: i) a patient-actuated device; ii) control software; iii) a practitioner graphical interface; iv) virtual reality software; and v) training software. The system can be used for measurement of ankle kinematics and balance function as well as for retraining motor control of the ankle, and can be used in either a sitting or standing position to accommodate early and late phases of rehabilitation training. We report here the details of the various design features and initial testing of the device.

We describe the development and preliminary testing of a low cost virtual reality system that patients with stroke or other neurological impairments could use independently in the home on a personal computer to improve upper extremity motor function, including hand and finger control. The system would help meet the needs of the rising number of patients with stroke with impaired hand function. We introduce the concept of a Multiple User Virtual Environment for Rehabilitation (MUVER). The MUVER has three components: the low cost P5 Glove (tracks arm, hand and finger movements), the open source Panda3D game engine, and laboratory created software. A unique aspect of the MUVER design is the system's capability for four types of multiple user interactions: competition, cooperation, counter-operative, and mixed. Such virtual interactions may help to increase patients' motivation to improve and possibly alleviate feelings of social isolation for those who remain homebound. Thus far, a proof of concept virtual environment that uses competitive interaction has been created and tested with six healthy subjects.

This paper presents the design, fabrication, control and testing of the third generation prototype of a novel, one degree of freedom (DOF) Variable Resistance Hand Device (VRHD) that was designed for isotonic, isokinetic, and variable resistance grasp and release exercises. Its principle functionality is derived from an electro-rheological fluid based controllable damper that allows continuously variable modulation of dynamic resistance throughout its stroke. The VRHD system consists of the patient actuated device, the control electronics and software, the practitioner graphical interface and the patient's virtual reality game software. VRHD was designed and experimentally shown to be fully Magnetic Resonance Imaging (MRI) compatible so that it can be used in brain MR imaging during handgrip rehabilitation.

There is a need for new pedagogical strategies to educate the current generation of engineering students who are still typically taught using standard lecture practices. The desire to address complex technological and social issues in an engaged manner inspired the development of a prototype board game created to raise the awareness of environmental issues in engineering. As part of a graduate thesis, the board game Shortfall was designed for in-class play by undergraduate and graduate engineering students and business students. The game structure was based on team competition of "companies" in the automobile supply chain, with the game objective set to achieve the highest profit. In 2005, it was evident that developments in digital technology allowed new opportunities to engage students in collaborative and active learning. A team of engineers, educators and designers further developed the board game with more in-depth scenarios and graphic organization. The game was then play tested and assessed learning and game play as an initial step in the process of developing a multi-player computer-based version of Shortfall.Student feedback from play testing, focus groups and surveys provided insights for redesigning the game for the computer platform. Two senior undergraduate engineering students in an independent study took these results and have created a prototype computer-based simulation designed as an experimental educational technology for an engineering course on environmentally benign manufacturing. This prototype was created to be the first computer-based step towards a fully networked multiplayer implementation. The transformation from board game to computer-based simulation presented many new challenges and tradeoffs, which are detailed in this paper. The goal was to maintain the core mechanics of the board game so that intellectual merit was not lost in translation while forging the first computer-based implementation.

We studied ocular motor function in 34 patients with motor neuron disease (MND) and in 18 age-matched controls. This included the latency, accuracy, and amplitude-velocity relationships of saccades. We also examined ocular pursuit, the slow phases of optokinetic nystagmus, and the ability to suppress the vestibulo-ocular reflex (VOR) with visual fixation of a head-mounted target. Five of the subjects with MND had pronounced parkinsonian features on neurologic examination. The nonparkinsonian MND subjects had normal ocular motor function for all measures. Most subjects suppressed the VOR completely. The parkinsonian-MND patients had impairment of both saccadic and pursuit eye movements, and one parkinsonian-MND patient with poor pursuit was unable to suppress the VOR. We conclude that ocular motor function is generally spared in MND. The occasional appearance of ocular motor dysfunction probably reflects the incidence of secondary abnormalities such as parkinsonism.

•A 62-year-old female with a history of right C3-C4 facet joint disease underwent unilateral radiofrequency denervation with fluoroscopically controlled placement of the electrode under general anesthesia. She awoke with dysphagia, aphonia, and neck swelling. She had undergone prior steroid injections at C3 and C4 for management of her chronic neck pain. On initial office evaluation, she had moderate dysphonia with a phonation time of 6.5 seconds. A dense right vocal fold paralysis was noted. Her Voice Handicap Index (VHI) was 42. Aphonia persisted through the first 3 months and gradually improved with intensive voice therapy.

Five hundred consecutive patients were evaluated for myasthenia gravis with repetitive stimulation of the median and ulnar nerves. Axillary nerve stimulation and repeated stimulation of wrist nerves following regional curare administration to the hand were performed when necessary. Abnormal responses were seen in 95% of 297 patients with generalized disease and in 35% of 54 patients with ocular disease, all of whom were clinically responsive to anticholinesterases. Identical responses were also seen in 32% of 124 patients with possible generalized disease, all of whom lacked clinical responsiveness to anticholinesterases. Abnormalities occurred following regional curare administration in 29% of 224 patients with normal responses during repetitive stimulation alone. This program for evaluating patients with suspected myasthenia gravis continues to be successful, safe, and practical.

A 16-year-old boy was seen for severe episodic muscle cramps and generalized myokymia, consistent with Isaacs's syndrome. Bilateral calf hypertrophy (46-cm calf circumference) and ankle areflexia were noted. He was treated with phenytoin sodium, 300 mg/day. Within three months there was marked decrease in myokymia, total relief of cramps, return of ankle reflexes, and 6-cm reduction in calf circumference. We suggest that the excess muscle activity in Isaacs's syndrome may be responsible for the associated phenomena of muscle hypertrophy and areflexia.