Quantifying dosage of physical therapy using lower body kinematics: a longitudinal pilot study on early post-stroke individuals.

BACKGROUND: While therapy is an important part of the recovery process, there is a lack of quantitative data detailing the "dosage" of therapy received due to the limitations on in/outpatient accessibility and mobility. Advances in wearable sensor technology have allowed us to obtain an unprecedented glimpse into joint-level kinematics in an unobtrusive manner. The objective of this observational longitudinal pilot study was to evaluate the relations between lower body joint kinematics during therapy and functional gait recovery over the first three months after stroke. METHODS: Six individuals with subacute stroke (< 1 month) were monitored for a total of 59 one-hour physical therapy sessions including gait and non-gait activities. Participants donned a heart rate monitor and an inertial motion capture system to measure full lower body joint kinematics during each therapy session. Linear mixed regression models were used to examine relations between functional gait recovery (speed) and activity features including total joint displacements, defined as amount of motion (AoM), step number, change in heart rate (∆HR), and types of tasks performed. RESULTS: All activity features including AoM, step number, types of tasks performed (all p < 0.01), and ∆HR (p < 0.05) showed strong associations with gait speed. However, AoM (R2 = 32.1%) revealed the greatest explained variance followed by step number (R2 = 14.1%), types of tasks performed (R2 = 8.0%) and ∆HR (R2 = 5.8%). These relations included both gait and non-gait tasks. Contrary to our expectations, we did not observe a greater relation of functional recovery to motion in the impaired limb (R2 = 27.8%) compared to the unimpaired limb (R2 = 32.9%). CONCLUSIONS: This proof-of-concept study shows that recording joint kinematics during gait therapy longitudinally after stroke is feasible and yields important information for the recovery process. These initial results suggest that compared to step number, more holistic outcome measures such as joint motions may be more informative and help elucidate the dosage of therapy.

Accuracy of palpation-directed intra-articular glenohumeral injection confirmed by magnetic resonance arthrography.

PURPOSE: The aim of this study was to determine the accuracy of anatomic palpation-directed injections in the office setting. METHODS: Two hundred twenty-six shoulders in 208 patients were studied using a 0.2-Tesla extremity scanner after the injection of gadolinium-diethylene triamine pentaacetic acid-saline. All patients were injected in a sterile fashion by a single board-certified shoulder surgeon using an anterior approach by palpating the rotator interval anterior to the acromioclavicular joint and angling the needle 45° lateral and 45° caudad. All injections, successful or otherwise, were single injections. Magnetic resonance (MR) arthrograms were retrospectively read by 2 musculoskeletal fellowship-trained, board certified radiologists to determine whether the injection was in the glenohumeral joint. RESULTS: Two hundred one of the 226 injections were successful (88.9%). Of the 25 unsuccessful injections, the contrast material extravasated out of the capsule in 5 cases and into the subscapularis tendon in 10 cases. The contrast material was injected into the subacromial space in 9 cases, into the rotator interval fat in 9 cases, and into extracapsular tissue in 6 cases. There was insufficient volume of contrast material in 10 cases. The accuracy rate was 88.9%. There were no complications. CONCLUSIONS: The palpation-directed rotator interval anterior approach technique for intra-articular glenohumeral MR arthrogram injections performed by a single surgeon was 88.9% accurate. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Between-limb difference in peak knee flexion angle can identify persons post-stroke with Stiff-Knee gait.

BACKGROUND: Stiff-Knee gait affects 25-75 % of individuals with post-stroke gait impairment and is typically defined as reduced swing phase knee flexion. Different studies use various measures to identify Stiff-Knee gait, such as peak swing knee flexion angle, timing of peak knee flexion, knee range of motion, and ankle push-off acceleration, leading to inconsistent results. METHODS: This study used univariate cluster analysis to examine the independence, consistency, validity, and accuracy of different definitions in 50 post-stroke individuals (24 with and 26 without Stiff-Knee gait), as determined by a physiatrist. Spearman's rank correlation was used for correlation analysis, and five clustering techniques along with clinician evaluations were used for validity analysis. FINDINGS: Correlation analysis showed that peak knee flexion timing and knee hyperextension are poorly correlated with reduced swing-phase knee flexion angle (ρ = -0.09 and ρ = -0.26 respectively). Validity analysis indicated that the between-limb difference in peak swing knee flexion angle and peak swing knee flexion angle at self-selected gait speeds were the most valid differentiators. At the fastest comfortable gait speed, the between-limb difference of peak knee flexion angle had the highest sensitivity, lowest specificity, and highest F1 scores. INTERPRETATION: We determined thresholds of less than 44.3° for peak swing knee flexion angle and greater than 17.0° for the between-limb difference of peak knee flexion angle identify Stiff-Knee gait during self-selected walking. We recommend using the difference in peak swing knee flexion angle between limbs to diagnose post-stroke Stiff-Knee gait due to its robustness to changes in gait speed.

Impact of Gravity Compensation on Upper Extremity Movements in Harmony Exoskeleton.

Robots have been used to offset the limb weight through gravity compensation in upper body rehabilitation to delineate the effects of loss of strength and loss of dexterity, which are two common forms of post-stroke impairments. In this paper, we explored the impact of this anti-gravity support on the quality of movement during reaching and coordinated arm movements in a pilot study with two participants with chronic stroke. The subjects donned the Harmony exoskeleton which supported proper shoulder coordination in addition to providing gravity compensation. Participants had previously taken part in seven one-hour sessions with the Harmony exoskeleton, performing six sets of passive-stretching and active exercises. Pre- and post-training sessions included assessments of two separate tasks, planar reaching and a set of six coordinated arm movements, in two conditions, outside of and supported by the exoskeleton. The movements were recorded using an optical motion capture system and analyzed using spectral arc length (SPARC) and straight line deviation to quantify movement smoothness and quality. We observed that gravity compensation resulted in an increased smoothness for the subject with high level of impairment whereas compensation resulted in a reduction in smoothness for the subject with low level of impairment in the reaching task. Both participants demonstrated better coordination of the shoulder-arm joint with gravity compensation. This result motivates further studies into the role of gravity compensation during coordinated movement training and rehabilitation interventions.

The predictability of serum anti-Müllerian level in IVF/ICSI outcomes for patients of advanced reproductive age.

BACKGROUND: The role of serum anti-Müllerian hormone (AMH) as predictor of in-vitro fertilization outcomes has been much debated. The aim of the present study is to investigate the practicability of combining serum AMH level with biological age as a simple screening method for counseling IVF candidates of advanced reproductive age with potential poor outcomes prior to treatment initiation. METHODS: A total of 1,538 reference patients and 116 infertile patients aged greater than or equal to 40 years enrolled in IVF/ICSI cycles were recruited in this retrospective analysis. A reference chart of the age-related distribution of serum AMH level for Asian population was first created. IVF/ICSI patients aged greater than or equal to 40 years were then divided into three groups according to the low, middle and high tertiles the serum AMH tertiles derived from the reference population of matching age. The cycle outcomes were analyzed and compared among each individual group. RESULTS: For reference subjects aged greater than or equal to 40 years, the serum AMH of the low, middle and high tertiles were equal or lesser than 0.48, 0.49-1.22 and equal or greater than 1.23 ng/mL respectively. IVF/ICSI patients aged greater than or equal to 40 years with AMH levels in the low tertile had the highest cycle cancellation rate (47.6%) with zero clinical pregnancy. The nadir AMH level that has achieved live birth was 0.56 ng/mL, which was equivalent to the 36.4th percentile of AMH level from the age-matched reference group. The optimum cut-off levels of AMH for the prediction of nonpregnancy and cycle cancellation were 1.05 and 0.68 ng/mL, respectively. CONCLUSIONS: Two criteria: (1) age greater than or equal to 40 years and (2) serum AMH level in the lowest tertile (equal or lesser than 33.3rd percentile) of the matching age group, may be used as markers of futility for counseling IVF/ICSI candidates.

Does kinematic gait quality improve with functional gait recovery? A longitudinal pilot study on early post-stroke individuals.

Typical clinical gait outcomes mostly focus on function; only sparse information exists on gait quality, i.e. symmetry or more natural gait patterns. It remains unclear whether functional gait recovery improves with gait quality, or whether these are two independent processes. The objective of this observational pilot study is to examine whether the gait quality improves with gait function (i.e. speed) over the course of early recovery. Full lower body gait kinematics were measured longitudinally in a clinical environment using wearable inertial measurement units. We recorded six individuals with subacute stroke (<1 month) for a total of 56 physical therapy sessions over the initial recovery stage of 12 weeks. We examined relations between gait symmetry in spatiotemporal, limb and joint kinematic parameters compared to gait function. We observed that overall gait symmetry improved with walking speed, but limb and joint kinematic parameters remained asymmetric at the maximum level of recovery (both p < 0.01). We also found that limb kinematic parameters (R2 = 41.9%) of the impaired side was preferentially associated with functional gait recovery over joint kinematics (R2 = 33.1%). These data suggest that our pilot cohort did not achieve "true" gait recovery despite achieving typical measures of recovery in gait speed and spatiotemporal symmetry. These initial results illustrate the multifaceted nature of recovery and justify further research on monitoring gait quality with a larger clinical study, providing insight for more effective training regimens.

Exploring the Capabilities of Harmony for Upper-Limb Stroke Therapy.

Harmony is a bimanual upper-limb exoskeleton designed for post-stroke rehabilitation. It moves the subject's shoulders and arms through their entire ranges of motion while maintaining natural coordination, is capable of force/torque control of each joint, and is equipped with sensors to measure motions and interaction forces. With these capabilities Harmony has the potential to assess motor function and create individualized therapy regimens. As a first step, five stroke survivors underwent rehabilitation sessions practicing multijoint movements with the device. Each participant performed a total of 1130 motions over seven hours of therapy with no adverse effects reported by participants or the attending therapist, supporting the suitability of Harmony for use in a clinical setting. Donning and doffing time averaged 3.5 minutes and decreased with therapist experience. Reported levels of stress, anxiety, and pain indicate that the Harmony safely assisted in the completion of the trained movements and has great potential to motivate and engage patients. We developed a novel methodology for assessing coordination capability and results from the study indicate that Harmony can enable therapists to identify neuromuscular weakness and maladaptive coordination patterns and develop targeted interventions to address these aspects of upper-limb function. The results suggest Harmony's feasibility and show promising improvements, motivating future study to gain statistical support.

Platelet-activating factor increases prostaglandin E(2) release from astrocyte-enriched cortical cell cultures.

The phospholipid mediator platelet-activating factor (PAF) increased the release of prostaglandin E(2) (PGE(2)) from astrocyte-enriched cortical cell cultures in a concentration- and time-dependent manner. The nonhydrolyzable PAF analog methylcarbamyl-PAF (mc-PAF), the PAF intermediate lyso-PAF, and arachidonic acid (AA) also produced this effect. In contrast, phosphatidlycholine (PC) and lyso-PC, lipids that are structurally similar to PAF and lyso-PAF, had no effect on PGE(2) production, suggesting that PAF-induced PGE(2) release is not the consequence of nonspecific phospholipid-induced membrane perturbation. Antagonism of intracellular PAF binding sites completely abolished the ability of mc-PAF and lyso-PAF to mobilize PGE(2,) and attenuated the AA effect. Antagonism of the G-protein-coupled PAF receptor in plasma membranes had no significant effect on mc-PAF, lyso-PAF or AA-induced PGE(2) release. Based on the present findings, we hypothesize that intracellular PAF is a physiologic stimulus of PGE(2) production in astrocytes.

Effect of a 5-HT(2C) serotonin agonist, dexnorfenfluramine, on amyloid precursor protein metabolism in guinea pigs.

Stimulation of serotonin receptor subtypes 5-HT(2A) or 5-HT(2C) in stably transfected 3T3 cells by dexnorfenfluramine (DEXNOR) or serotonin increases secretion of the APP metabolite APP(s). It is not known whether activation of these receptors can also affect APP metabolism in vivo. We examined the effects of a single intraperitoneal (i.p.) injection of DEXNOR on APP(s) levels in cerebrospinal fluid (CSF) of guinea pigs. These levels were significantly (P<0.05) increased by a single dose of DEXNOR (1-4 mg/kg); those of the APP metabolites Abeta(1-40) and Abeta(1-42) were unaffected. The DEXNOR-induced (1 mg/kg) increases in CSF APP(s) were suppressed by ritanserin (1 mg/kg) but not by ketanserin (2 mg/kg). When given alone, ritanserin did not affect CSF levels of APP(s), Abeta(1-40), or Abeta(1-42). Chronic treatment with DEXNOR for 9 days (1 mg/kg bid, i.p.) increased CSF APP(s) levels, measured 2 h after the last injection (P<0.05), and decreased those of CSF Abeta(1-42) (P<0.05). Neither hippocampal nor cortical levels of the APP holoprotein (APP(h)), nor body weight, were affected by DEXNOR. Chronic administration of mCPP (1-(m-chlorophenyl)piperazine) (2 mg/kg bid, i.p.), a 5-HT(2B/2C) agonist, for 9 days also increased CSF APP(s) levels (P<0.5) when measured 2 h after the drug's last administration; hippocampal and cortical APP(h) levels were unaffected. However, mCPP also caused a significant decrease in body weight gain. These data indicate that the pharmacological activation of 5-HT(2C) receptors can stimulate CSF APP(s) secretion and reduce Abeta production in vivo. Hence 5-HT(2C) receptors, which apparently are localized to the brain, may represent useful targets for the development of treatments for Alzheimer's disease.

Prostaglandin E2 regulates amyloid precursor protein expression via the EP2 receptor in cultured rat microglia.

We investigated the effects of prostaglandin E2 (PGE2) on amyloid precursor protein (APP) expression in cultured rat microglia. PGE2 treatment significantly increased the expression of APP holoprotein and was associated with an elevation in cyclic AMP (cAMP). Direct activation of adenylate cyclase with forskolin also increased APP expression. Co-treatment of microglia with PGE2 and the PKA inhibitor H-89 suppressed the overexpression of APP caused by PGE2 alone. The prostaglandin EP2 receptor is known to be positively coupled to cAMP production. Stimulation of the EP2 receptor with butaprost increased APP holoprotein, whereas co-incubation of the cells with PGE(2) and the EP2 receptor antagonist AH-6809 blocked the effect of PGE2 on APP expression. These data suggest that PGE2 is able to regulate the expression of APP, and that this effect may be mediated by the EP2 receptor and the cAMP signaling cascade.

Long oblique distal osteotomy of the fifth metatarsal for correction of tailor's bunion: a retrospective review.

A long-term retrospective review of a long oblique distal osteotomy of the fifth metatarsal for correction of a tailor's bunion deformity is presented. The technique, results, and follow-up of this procedure are described. The long oblique distal osteotomy was performed on 25 feet on 16 patients. Follow-up ranged from 11 to 110 months with an average of 64.4 months. The average preoperative intermetatarsal 4-5 angle and lateral deviation angle improved from 10.88 degrees and 4.24 degrees, respectively, to 5.52 degrees and -4.24 degrees postoperatively, respectively. A modified scoring scale for lesser metatarsal procedures was used, showing an average postoperative score of 94 out of 100 possible points. Subjectively, 96% (24 of 25) of feet that underwent surgery were rated as excellent or good. Complications included one patient with paresthesias, one soft-tissue infection, and 2 patients had irritation from screws. The authors conclude that the long oblique distal osteotomy is a viable alternative in the correction of tailor's bunion deformity.