Single institution experience with efgartigimod in patients with myasthenia gravis: Patient selection, dosing schedules, treatment response, and adverse events.

INTRODUCTION/AIMS: Efgartigimod is a neonatal Fc receptor blocker and was the first approved medication in its class for the treatment of generalized myasthenia gravis (gMG). As a novel therapy, little is known about the use of efgartigimod in clinical practice. This study aims to describe how efgartigimod is being incorporated into the current therapeutic landscape of MG. METHODS: We reviewed the charts of 17 patients with gMG treated with efgartigimod at the University of Pennsylvania between January 2022 and June 2023. RESULTS: Efgartigimod was selected mainly for patients who were treatment refractory, had side effects to other treatments, and/or required quick improvement in their symptoms. All patients had been previously treated with at least one medication for MG and had an average baseline Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 9.1. The patients treated with efgartigimod improved their MG-ADL score by an average of 5.5 points at 3 months (p < .001) and 7.1 points by 6 months (p < .001). Forty percent of patients achieved minimal symptom expression. Adverse events (AEs) were reported in 43.7% of patients on efgartigimod, the most common being mild infection (urinary tract infection and thrush). There were no serious AEs. DISCUSSION: This study found efgartigimod to be efficacious, well tolerated, and safe in patients with MG. Efgartigimod should be considered as an add-on therapy, a bridge therapy, or as a monotherapy if patients have difficulty tolerating other treatments.

Superimposed Neuroinvasive Coccidioidomycosis and West Nile Virus Infection.

A 58-year-old man with recently diagnosed coccidioidal meningitis presented to the ED with a five-day history of headache, photopsia, blurred vision, and worsening encephalopathy. His coccidioidal meningitis had responded well to fluconazole therapy, but three weeks later, he developed acute symptomatic worsening. Unfortunately, his clinical worsening coincided with Arizona's worst seasonal West Nile Virus (WNV) outbreak. He was ultimately found to have WNV neuroinvasive disease. Concurrent coccidioidal and WNV neuroinvasive diseases have not been described in the literature. Fortunately, he improved quickly to his normal baseline without neurologic deficits with supportive therapy for his WNV neuroinvasive disease and remains on lifelong antifungal therapy for coccidioidal meningitis.

The impact of ankle-foot orthosis's plantarflexion resistance on knee adduction moment in people with chronic stroke.

BACKGROUND: An ankle-foot orthosis (AFO) is used to assist gait of people with chronic stroke. It is widely accepted that AFO's plantarflexion resistance affects sagittal knee moments during their gait. However, its effect on the coronal knee moment remains unclear. This study aimed to examine the effects of varying articulated AFO's plantarflexion resistance on knee adduction moment in people with chronic stroke. METHODS: Ten people with chronic stroke participated in this study. Gait performance was measured using a Vicon 3-dimensional motion capture system and a Bertec split-belt instrumented treadmill. The participants walked on the treadmill wearing an articulated AFO whose plantarflexion resistance could be systematically adjusted. The ankle joints were set to four distinct levels of plantarflexion resistance (S1 < S2 < S3 < S4). The coronal ankle and knee joint moment, center of pressure, and ground reaction force were analyzed using Visual3D. RESULTS: The external knee adduction moment increased significantly ( P < .001) and the position of the center of pressure trajectory shifted significantly ( P = .003) in the medial direction as the plantarflexion resistance of the AFO was increased from the least resistive condition (S1) to the most resistive condition (S4). The maximum knee adduction moment (median [interquartile range]) was S1: 0.097 (-0.012 to 0.265) Nm/kg; S2: 0.136 (0.040 to 0.287) Nm/kg; S3: 0.160 (0.465 to 0.289) Nm/kg; and S4: 0.192 (0.080 to 0.288) Nm/kg. CONCLUSIONS: This study demonstrated that varying AFO's plantarflexion resistance altered the knee adduction moment, likely by altering the center of pressure trajectory while walking, in people with chronic stroke.

Effect of plantarflexion resistance of an ankle-foot orthosis on ankle and knee joint power during gait in individuals post-stroke.

Plantarflexion resistance of an ankle-foot orthosis (AFO) plays an important role to prevent foot-drop, but its impact on push-off has not been well investigated in individuals post-stroke. The aim of this study was to investigate the effect of plantarflexion resistance of an articulated AFO on ankle and knee joint power of the limb wearing the AFO in individuals post-stroke. Gait analysis was performed on 10 individuals with chronic stroke using a Vicon 3-dimensional motion capture system and a Bertec split-belt instrumented treadmill. They walked on the treadmill under 4 plantarflexion resistance levels (S1 < S2

Contribution of ankle-foot orthosis moment in regulating ankle and knee motions during gait in individuals post-stroke.

BACKGROUND: Ankle-foot orthosis moment resisting plantarflexion has systematic effects on ankle and knee joint motion in individuals post-stroke. However, it is not known how much ankle-foot orthosis moment is generated to regulate their motion. The aim of this study was to quantify the contribution of an articulated ankle-foot orthosis moment to regulate ankle and knee joint motion during gait in individuals post-stroke. METHODS: Gait data were collected from 10 individuals post-stroke using a Bertec split-belt instrumented treadmill and a Vicon 3-dimensional motion analysis system. Each participant wore an articulated ankle-foot orthosis whose moment resisting plantarflexion was adjustable at four levels. Ankle-foot orthosis moment while walking was calculated under the four levels based on angle-moment relationship of the ankle-foot orthosis around the ankle joint measured by bench testing. The ankle-foot orthosis moment and the joint angular position (ankle and knee) relationship in a gait cycle was plotted to quantify the ankle-foot orthosis moment needed to regulate the joint motion. FINDINGS: Ankle and knee joint motion were regulated according to the amount of ankle-foot orthosis moment during gait. The ankle-foot orthosis maintained the ankle angular position in dorsiflexion and knee angular position in flexion throughout a gait cycle when it generated moment from -0.029 (0.011) to -0.062 (0.019) Nm/kg (moment resisting plantarflexion was defined as negative). INTERPRETATIONS: Quantifying the contribution of ankle-foot orthosis moment needed to regulate lower limb joints within a specific range of motion could provide valuable criteria to design an ankle-foot orthosis for individuals post-stroke.

Reduction of genu recurvatum through adjustment of plantarflexion resistance of an articulated ankle-foot orthosis in individuals post-stroke.

BACKGROUND: Genu recurvatum (knee hyperextension) is a common issue for individuals post-stroke. Ankle-foot orthoses are used to improve genu recurvatum, but evidence is limited concerning their effectiveness. Therefore, the aim of this study was to investigate the effect of changing the plantarflexion resistance of an articulated ankle-foot orthosis on genu recurvatum in patients post-stroke. METHODS: Gait analysis was performed on 6 individuals post-stroke with genu recurvatum using an articulated ankle-foot orthosis whose plantarflexion resistance was adjustable at four levels. Gait data were collected using a Bertec split-belt instrumented treadmill in a 3-dimensional motion analysis laboratory. Gait parameters were extracted and plotted for each subject under the four plantarflexion resistance conditions of the ankle-foot orthosis. Gait parameters included: a) peak ankle plantarflexion angle, b) peak ankle dorsiflexion moment, c) peak knee extension angle and d) peak knee flexion moment. A non-parametric Friedman test was performed followed by a post-hoc Wilcoxon Signed-Rank test for statistical analyses. FINDINGS: All the gait parameters demonstrated statistically significant differences among the four resistance conditions of the AFO. Increasing the amount of plantarflexion resistance of the ankle-foot orthosis generally reduced genu recurvatum in all subjects. However, individual analyses showed that the responses to the changes in the plantarflexion resistance of the AFO were not necessarily linear, and appear unique to each subject. INTERPRETATIONS: The plantarflexion resistance of an articulated AFO should be adjusted to improve genu recurvatum in patients post-stroke. Future studies should investigate what clinical factors would influence the individual differences.

Direct measurement of plantarflexion resistive moments and angular positions of an articulated ankle-foot orthosis while walking in individuals post stroke: A preliminary study.

The plantarflexion resistive moments of an articulated ankle-foot orthosis play an important role in improving gait in individuals post stroke. However, the evidence regarding their magnitude required from the articulated ankle-foot orthosis to improve walking is still limited. Therefore, the primary aim of this study was to directly measure the plantarflexion resistive moments and the joint angular positions while walking using a prototype instrumented articulated ankle-foot orthosis in five individuals post stroke. The secondary aim was to investigate their moment-angle relationship by changing its preset plantarflexion stiffness. Each subject was fitted with the instrumented articulated ankle-foot orthosis and walked on a treadmill under four different preset plantarflexion stiffness conditions (0.35 N·m/°, 0.51 N·m/°, 0.87 N·m/°, and 1.27 N·m/°). For each subject, the plantarflexion resistive moments and the joint angular positions of five continuous gait cycles were extracted and averaged for each condition. Data were plotted and presented as case series. Both plantarflexion resistive moments and joint angular positions of the ankle-foot orthosis changed according to the preset plantarflexion stiffness in all subjects. Using the instrumented articulated ankle-foot orthosis could potentially advance the understanding of the biomechanics of an ankle-foot orthosis, as well as contribute to more evidence-based orthotic care of patients.

The effect of changing plantarflexion resistive moment of an articulated ankle-foot orthosis on ankle and knee joint angles and moments while walking in patients post stroke.

BACKGROUND: The adjustment of plantarflexion resistive moment of an articulated ankle-foot orthosis is considered important in patients post stroke, but the evidence is still limited. Therefore, the aim of this study was to investigate the effect of changing the plantarflexion resistive moment of an articulated ankle-foot orthosis on ankle and knee joint angles and moments in patients post stroke. METHODS: Gait analysis was performed on 10 subjects post stroke under four different plantarflexion resistive moment conditions using a newly designed articulated ankle-foot orthosis. Data were recorded using a Bertec split-belt instrumented treadmill in a 3-dimensional motion analysis laboratory. FINDINGS: The ankle and knee sagittal joint angles and moments were significantly affected by the amount of plantarflexion resistive moment of the ankle-foot orthosis. Increasing the plantarflexion resistive moment of the ankle-foot orthosis induced significant decreases both in the peak ankle plantarflexion angle (P<0.01) and the peak knee extension angle (P<0.05). Also, the increase induced significant increases in the internal dorsiflexion moment of the ankle joint (P<0.01) and significantly decreased the internal flexion moment of the knee joint (P<0.01). INTERPRETATION: These results suggest an important link between the kinematic/kinetic parameters of the lower-limb joints and the plantarflexion resistive moment of an articulated ankle-foot orthosis. A future study should be performed to clarify their relationship further so that the practitioners may be able to use these parameters as objective data to determine an optimal plantarflexion resistive moment of an articulated ankle-foot orthosis for improved orthotic care in individual patients.

Accuracy and feasibility of high-speed dual fluoroscopy and model-based tracking to measure in vivo ankle arthrokinematics.

The relationship between altered tibiotalar and subtalar kinematics and development of ankle osteoarthritis is unknown, as skin marker motion analysis cannot measure articulations of each joint independently. Here, we quantified the accuracy and demonstrated the feasibility of high-speed dual fluoroscopy (DF) to measure and visualize the three-dimensional articulation (i.e., arthrokinematics) of the tibiotalar and subtalar joints. Metal beads were implanted in the tibia, talus and calcaneus of two cadavers. Three-dimensional surface models of the cadaver and volunteer bones were reconstructed from computed tomography images. A custom DF system was positioned adjacent to an instrumented treadmill. DF images of the cadavers were acquired during maximal rotation about three axes (dorsal-plantar flexion, inversion-eversion, internal-external rotation) and simulated gait (treadmill at 0.5 and 1.0 m/s). Positions of implanted beads were tracked using dynamic radiostereometric analysis (DRSA). Bead locations were also calculated using model-based markerless tracking (MBT) and compared, along with joint angles and translations, to DRSA results. The mean positional difference between DRSA and MBT for all frames defined bias; standard deviation of the difference defined precision. The volunteer was imaged with DF during treadmill gait. From these movements, joint kinematics and tibiotalar and subtalar bone-to-bone distance were calculated. The mean positional and rotational bias (±standard deviation) of MBT was 0.03±0.35 mm and 0.25±0.81°, respectively. Mean translational and rotational precision was 0.30±0.12 mm and 0.63±0.28°, respectively. With excellent measurement accuracy, DF and MBT may elucidate the kinematic pathways responsible for osteoarthritis of the tibiotalar and subtalar joints in living subjects.

Age-related difference in postural control during recovery from posterior and anterior perturbations.

Decreased reactive postural responses in elderly adults may place them at increased risk for falls and related injuries. The first step in addressing the high rate of falls in the elderly population is to determine a baseline for postural response in healthy young and healthy elderly individuals. To determine these age-related differences in reactive postural responses during recovery from posterior and anterior perturbations, we used the tether-release method in conjunction with a motion analysis system to evaluate overall movement latencies, overall movement amplitude and velocity, and joint-specific amplitude and velocity in healthy young (n = 10, mean age=25 ± 5) and healthy elderly participants (n = 10, mean age = 67 ± 6). During posterior perturbations, healthy elderly participants had increased recovery time (P = 0.01) and ratio of center of mass to step length (P = 0.013) when compared with young participants. Elderly participants also had decreased step length (P = 0.006), peak COM velocity (P = 0.01), peak knee flexion angle (P = 0.002), and decreased hip (P = 0.005) and knee (P = 0.0005) average angular velocity when compared with young participants. We conclude that these movement deficiencies at the hip and knee limited the length of the recovery step. With this restricted step, elderly participants could not achieve adequate mechanical advantage to counteract the displacement of their COM using a single step. During anterior perturbations, elderly participants did not exhibit any significant differences compared to young participants in overall movement variables. This understanding of postural responses in healthy individuals is clinically relevant to the development of rehabilitation programs for individuals at high fall risk.

The effect of ankle-foot orthosis plantarflexion stiffness on ankle and knee joint kinematics and kinetics during first and second rockers of gait in individuals with stroke.

BACKGROUND: Stiffness of an ankle-foot orthosis plays an important role in improving gait in patients with a history of stroke. To address this, the aim of this case series study was to determine the effect of increasing plantarflexion stiffness of an ankle-foot orthosis on the sagittal ankle and knee joint angle and moment during the first and second rockers of gait. METHODS: Gait data were collected in 5 subjects with stroke at a self-selected walking speed under two plantarflexion stiffness conditions (0.4Nm/° and 1.3Nm/°) using a stiffness-adjustable experimental ankle-foot orthosis on a Bertec split-belt fully instrumented treadmill in a 3-dimensional motion analysis laboratory. FINDINGS: By increasing the plantarflexion stiffness of the ankle-foot orthosis, peak plantarflexion angle of the ankle was reduced and peak dorsiflexion moment was generally increased in the first rocker as hypothesized. Two subjects demonstrated increases in both peak knee flexion angle and peak knee extension moment in the second rocker as hypothesized. The two subjects exhibited minimum contractility during active plantarflexion, while the other three subjects could actively plantarflex their ankle joint. INTERPRETATION: It was suggested that those with the decreased ability to actively plantarflex their ankle could not overcome excessive plantarflexion stiffness at initial contact of gait, and as a result exhibited compensation strategies at the knee joint. Providing excessively stiff ankle-foot orthoses might put added stress on the extensor muscles of the knee joint, potentially creating fatigue and future pathologies in some patients with stroke.

Effects of dopamine replacement therapy on lower extremity kinetics and kinematics during a rapid force production task in persons with Parkinson disease.

Postural instability appears to be a dopamine resistance motor deficit in persons with Parkinson disease (PD); however, little is known about the effects of dopamine replacement on the relative biomechanical contributions of individual lower extremity joints during postural control tasks. To gain insight, we examined persons with PD using both clinical and laboratory measures. For a clinical measure of motor severity we utilized the Unified Parkinson Disease Rating Scale motor subsection during both OFF and ON medication conditions. For the laboratory measure we utilized data gathered during a rapid lower extremity force production task. Kinematic and kinetic variables at the hip, knee, and ankle were gathered during a counter movement jump during both OFF and ON medication conditions. Sixteen persons with PD with a median Hoehn and Yahr severity of 2.5 completed the study. Medication resulted in significant improvements of angular displacement for the hip, knee, and ankle. Furthermore, significant improvements were revealed only at the hip for peak net moments and average angular velocity compared to the OFF medication condition. These results suggest that dopamine replacement medication result in decreased clinical motor disease severity and have a greater influence on kinetics and kinematics proximally. This proximally focused improvement may be due to active recruitment of muscle force and reductions in passive restraint during lower extremity rapid force production.