Radiofrequency Ablation of the Infrapatellar Branch of the Saphenous Nerve for the Treatment of Chronic Anterior Inferomedial Knee Pain.

INTRO: Genicular nerve radiofrequency ablation (GNRFA) is an effective treatment for chronic knee pain related to osteoarthritis. It is often utilized when conservative management has failed and patients wish to avoid arthroplasty, are poor surgical candidates due to comorbid medical conditions, or in those suffering from persistent pain after arthroplasty. The classic targets for GNRFA include the superior lateral genicular nerve, superior medial genicular nerve, and inferior medial genicular nerve but multiple anatomic studies have demonstrated additional sensory innervation to the knee. OBJECTIVE: In this research article, we propose an image-guided technique that can safely target the infrapatellar branch of the saphenous nerve which also provides sensory innervation to the anterior capsule. PROPOSAL: The proposed technique includes variations for conventional bipolar radiofrequency ablation, cooled radiofrequency ablation, dual-tined bipolar radiofrequency ablation, and monopolar radiofrequency ablation using a long axis approach. The described technique is based on updated anatomic studies and takes into account safety concerns such as thermal risk to the skin and/or pes anserine tendons and breaching of the synovial cavity. CONCLUSION: Future clinical research should be performed to confirm the safety and effectiveness of this specific approach.

Functions necessary for gait independence in patients with stroke: A study using decision tree.

BACKGROUND: Little is known about the existence and impact of interactions among multiple impairments to gait independence. The purpose of this study is to reveal the interaction of physical functions and its impact on gait independence in stroke patients. METHODS: This retrospective study included 108 subacute stroke patients. We conducted a decision tree analysis to examine the existence of interactions in relation to gait independence among the gross motor function of lower limb, knee extension strength, sensory function, and trunk function. Further, we confirmed the existence and impact of interaction detected via the decision tree after adjusting for the effects of confounding factors using logistic regression. RESULTS: The knee extension strength and proprioception on the affected side were selected in the first and second level of the decision tree. In addition, the knee extension strength was selected in the third level. The interaction of the knee extension strength and proprioception on the affected side was significantly associated with gait independence, both before and after adjusting for age, visuospatial perception, and cognitive functions. CONCLUSIONS: Our results suggest that the interaction of the knee extension strength and proprioception on the affected side is strongly associated with gait independence in stroke patients.

Neuromuscular electrical stimulation increases serum brain-derived neurotrophic factor in humans.

Brain-derived neurotrophic factor (BDNF) plays several important roles in nervous system function including neuronal growth and plasticity. The purpose of the present study was to clarify whether neuromuscular electrical stimulation (NMES) and voluntary exercise to the same integrated force as by the NMES-induced exercise would enhance serum BDNF. Eleven healthy male subjects completed three interventions (NMES, voluntary exercise, and resting interventions) for 20 min on different days. In the NMES intervention, NMES was applied to the quadriceps femoris muscles. The stimulus intensity of NMES was progressively increased to the highest tolerated intensity during the experiment. In the voluntary exercise intervention, subjects performed an isometric knee-extension task; in this intervention, the target torque was calculated in accordance with the integrated force of knee extension obtained during the NMES intervention. In the resting intervention, subjects relaxed in a sitting posture. We measured serum BDNF, blood lactate, heart rate, oxygen uptake, respiratory ratio, and blood pressure. Serum BDNF was increased in the NMES (p = 0.003) and voluntary exercise interventions (p = 0.004) after each intervention. At the post-timepoint, serum BDNF in the NMES intervention was highest among all interventions (p = 0.038) and significantly higher than in the voluntary exercise (p = 0.036) and resting (p = 0.037) interventions. Our results showed that NMES was more effective for enhancing serum BDNF than voluntary exercise at least when employing the same method and integrated force.

Adductor Canal Block or Local Infiltrate Analgesia for Pain Control After Total Knee Arthroplasty? A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Total knee arthroplasty is a treatment option for debilitating arthritis. In the postoperative period, patients experience moderate to severe pain affecting the rehabilitation, hospital stay, and patient satisfaction. This study aims at utilizing current best evidence to determine whether adductor canal block (ACB) or periarticular injection (PAI) is a better modality for managing short-term postoperative pain and opioid consumption. METHODS: Embase, MEDLINE, HealthStar, Emcare, and PubMed were searched for randomized controlled trials from 1946 to August 2018, for literature addressing the comparison of ACB and PAI for pain management in the setting of total knee arthroplasty. A systematic review and meta-analysis were performed. RESULTS: Six studies were included in our meta-analysis. When examining the combined visual analog scale (VAS) pain values for each group, analysis demonstrated greater reduction in scores for the PAI group, and the difference was statistically significant (P = .001). When comparing the VAS scores of subgroups analyzed at specific periods in time, there was a trend toward lower VAS scores in subgroups analyzed at 24 hours and 48 hours postoperatively (at rest and at movement) in the PAI group. Overall opioid consumption was lower in the PAI group, with demonstrated statistical significance (P = .03). When comparing the postoperative subgroups, there was a trend toward decreased opioid use in the PAI group, with 13.25% less opioid use at 48 hours and 9.5% less opioid use at 24 hours. CONCLUSION: PAI could significantly improve postoperative pain and opioid consumption when compared with ACB. Additional, high-quality studies are required to further address this topic.

Stroke increases ischemia-related decreases in motor unit discharge rates.

Following stroke, hyperexcitable sensory pathways, such as the group III/IV afferents that are sensitive to ischemia, may inhibit paretic motor neurons during exercise. We quantified the effects of whole leg ischemia on paretic vastus lateralis motor unit firing rates during submaximal isometric contractions. Ten chronic stroke survivors (>1 yr poststroke) and 10 controls participated. During conditions of whole leg occlusion, the discharge timings of motor units were identified from decomposition of high-density surface electromyography signals during repeated submaximal knee extensor contractions. Quadriceps resting twitch responses and near-infrared spectroscopy measurements of oxygen saturation as an indirect measure of blood flow were made. There was a greater decrease in paretic motor unit discharge rates during the occlusion compared with the controls (average decrease for stroke and controls, 12.3 ± 10.0% and 0.1 ± 12.4%, respectively; P < 0.001). The motor unit recruitment thresholds did not change with the occlusion (stroke: without occlusion, 11.68 ± 5.83%MVC vs. with occlusion, 11.11 ± 5.26%MVC; control: 11.87 ± 5.63 vs. 11.28 ± 5.29%MVC). Resting twitch amplitudes declined similarly for both groups in response to whole leg occlusion (stroke: 29.16 ± 6.88 vs. 25.75 ± 6.78 Nm; control: 38.80 ± 13.23 vs 30.14 ± 9.64 Nm). Controls had a greater exponential decline (lower time constant) in oxygen saturation compared with the stroke group (stroke time constant, 22.90 ± 10.26 min vs. control time constant, 5.46 ± 4.09 min; P < 0.001). Ischemia of the muscle resulted in greater neural inhibition of paretic motor units compared with controls and may contribute to deficient muscle activation poststroke. NEW & NOTEWORTHY Hyperexcitable inhibitory sensory pathways sensitive to ischemia may play a role in deficient motor unit activation post stroke. Using high-density surface electromyography recordings to detect motor unit firing instances, we show that ischemia of the exercising muscle results in greater inhibition of paretic motor unit firing rates compared with controls. These findings are impactful to neurophysiologists and clinicians because they implicate a novel mechanism of force-generating impairment poststroke that likely exacerbates baseline weakness.

Later stages of diabetic neuropathy affect the complexity of the neuromuscular system at the knee during low-level isometric contractions.

INTRODUCTION: This study evaluates the complexity of force and surface electromyography (sEMG) during knee extension and flexion at low-level isometric contractions in individuals with different degrees of diabetic peripheral neuropathy (DPN). METHODS: Ten control and 38 diabetic participants performed isometric contractions at 10%, 20%, and 30% of maximal voluntary contraction. Knee force and multichannel sEMG from vastus lateralis (VL) and biceps femoris were acquired. The SD of force and sample entropy (SaEn) of both force and sEMG were computed. RESULTS: Participants with moderate DPN demonstrated high force-SD and low force-SaEn. Severely affected participants showed low SaEn in VL at all force levels. DISCUSSION: DPN affects the complexity of the neuromuscular system at the knee for the extension task during low-level isometric contractions, with participants in the later stages of the disease (moderate and severe) demonstrating most of the changes. Muscle Nerve 57: 112-121, 2018.

New device for nonvolitional evaluation of quadriceps force in ventilated patients.

INTRODUCTION: In mechanically ventilated patients, nonvolitional assessment of quadriceps weakness using femoral-nerve stimulation (twitch force) while the leg rests on a right-angle trapezoid or dangles from the bed edge is impractical. Accordingly, we developed a knee-support apparatus for use in ventilated patients. METHODS: Ninety subjects (12 ventilated patients, 28 ambulatory patients, and 50 healthy subjects) were enrolled. Twitches with leg-dangling, trapezoid, and knee-support setups were compared. RESULTS: Knee-support twitches were similar to trapezoid twitches but smaller than leg-dangling twitches (P < 0.0001). Inter- and intraoperator agreement was high for knee-support twitches at 1 week and 1 month. In ventilated patients, knee-support twitches were smaller than in healthy subjects and ambulatory patients (P < 0.004). DISCUSSION: The new knee-support apparatus allows accurate recording of quadriceps twitches. The ease of use in ventilated patients and excellent inter- and intraoperator agreement suggest that this technique is suitable for cross-sectional and longitudinal studies in critically ill patients. Muscle Nerve 57: 784-791, 2018.

Short vs. long pulses for testing knee extensor neuromuscular properties: does it matter?

PURPOSE: The present study aimed at comparing knee extensor neuromuscular properties determined with transcutaneous electrical stimulation using two pulse durations before and after a standardized fatigue protocol. METHODS: In the first sub-study, 19 healthy participants (ten women and nine men; 28 ± 5 years) took part to two separate testing sessions involving the characterization of voluntary activation (twitch interpolation technique), muscle contractility (evoked forces by single and paired stimuli), and neuromuscular propagation (M-wave amplitude from vastus lateralis and vastus medialis muscles) obtained at supramaximal intensity with a pulse duration of either 0.2 or 1 ms. The procedures were identical in the second sub-study (N = 11), except that neuromuscular properties were also evaluated after a standardized fatiguing exercise. Electrical stimulation was delivered through large surface electrodes positioned over the quadriceps muscle and a visual analog scale was used to evaluate the discomfort to paired stimuli evoked at rest. RESULTS: There was no difference between pulse durations in the estimates of voluntary activation, neuromuscular propagation, and muscle contractility both in the non-fatigued and fatigued states. The discomfort associated with supramaximal paired electrical stimuli was also comparable between the two pulse durations. CONCLUSIONS: It appears that 0.2- and 1-ms-long pulses provide a comparable evaluation of knee extensor neuromuscular properties.

Saphenous Nerve Block From Within the Knee Is Feasible for TKA: MRI and Cadaveric Study.

BACKGROUND: Surgeon-performed periarticular injections and anesthesiologist-performed femoral nerve or adductor canal blocks with local anesthetic are in common use as part of multimodal pain management regimens for patients undergoing TKA. However, femoral nerve blocks risk causing quadriceps weakness and falls, and anesthesiologist-performed adductor canal blocks are costly in time and resources and may be unreliable. We investigated the feasibility of a surgeon-performed saphenous nerve ("adductor canal") block from within the knee at the time of TKA. QUESTIONS/PURPOSES: (1) Can the saphenous nerve consistently be identified distally on MRI studies, and is there a consistent relationship between the width of the femoral transepicondylar axis (TEA) and the proximal (cephalad) location where the saphenous nerve emerges from the adductor canal? With these MRI data, we asked the second question: (2) Can we utilize this anatomic relationship to simulate a surgeon-performed intraoperative block of the distal saphenous nerve from within the knee with injections of dyes after implantation of trial TKA components in cadaveric lower extremity specimens? METHODS: A retrospective analysis of 94 thigh-knee MRI studies was performed to determine the relationship between the width of the distal femur at the epicondylar axis and the proximal location of the saphenous nerve after its exit from the adductor canal and separation from the superficial femoral artery. These studies, obtained from one hospital's MRI library, had to depict the saphenous nerve in the distal thigh and the femoral epicondyles and excluded patients younger than 18 years of age or with metal implants. These studies were performed to evaluate thigh and knee trauma or unexplained pain, and 55 had some degree of osteoarthritis. After obtaining these data, TKA resections and trial component implantation were performed, using a medial parapatellar approach, in 11 fresh cadaveric lower extremity specimens. There were six male and five female limbs from cadavers with a mean age of 70 years (range, 57-80 years) and mean body mass index of 20 kg/m (range, 15-26 kg/m) without known knee arthritis. Using a blunt-tipped 1.5-cm needle, we injected 10 mL each of two different colored solutions from inside the knee at two different locations and, after 30 minutes, dissected the femoral and saphenous nerves and femoral artery from the hip to the knee. Our endpoints were whether the saphenous nerve was bathed in dye and if the dye or needle was located in the femoral artery or vein. RESULTS: Based on the MRI analysis, the mean ± SD TEA was 75 ± 4 mm in females and 87 ± 4 mm in males. The saphenous nerve exited the adductor canal and was located at a mean of 1.5 ± 0.16 times the TEA width in females and a mean of 1.3 ± 0.13 times the TEA width in males proximal to the medial epicondyle. After placement of TKA trial components and injection, the proximal injection site solution bathed the saphenous nerve in eight of 11 specimens. In two cachectic female cadaver limbs, the dye was located posteriorly to the nerve in hamstring muscle. The proximal blunt needle and colored solution were directly adjacent to but did not penetrate the femoral artery in only one specimen. CONCLUSIONS: This study indicates, based on MRI measurements, cadaveric injections, and dissections, that a surgeon-performed injection of the saphenous nerve from within the knee after it exits from the adductor canal seems to be a feasible procedure. CLINICAL RELEVANCE: This technique may be a useful alternative to an ultrasound-guided block. A trial comparing surgeon- and anesthesiologist-performed nerve block should be considered to determine the clinical efficacy of this procedure.

Oblique incisions in hamstring tendon harvesting reduce iatrogenic injuries to the infrapatellar branch of the saphenous nerve.

PURPOSE: Iatrogenic injury to the infrapatellar branch of the saphenous nerve (IPBSN) is associated with many surgical interventions to the medial aspect of the knee, such as anterior cruciate ligament (ACL) reconstruction. Different types of surgical incisions during hamstring tendon harvesting for ACL reconstruction are related to a variable risk of IPBSN injury. This study aimed to evaluate the risk of iatrogenic IPBSN injury during hamstring tendon harvesting for ACL reconstruction with different incision techniques over the pes anserinus. METHODS: This study was performed on 100 cadavers. Vertical, horizontal, or oblique incisions were simulated on each cadaveric limb to determine the incidence of iatrogenic IPBSN injury. RESULTS: The vertical incision caused the IPBSN injury during hamstring tendon harvesting in 101 (64.7%), the horizontal incision in 78 (50.0%), and the oblique incision in 43 (27.6%) examined lower limbs. The calculated odds ratios (OR) for risk of injury in vertical versus horizontal and horizontal versus oblique incisions were 2.4 (95% CI 1.5-3.6) and 1.8 (95% 1.2-2.8), respectively. CONCLUSIONS: The vertical incision technique over the pes anserinus should be avoided during hamstring tendon harvesting for ACL reconstruction. The adoption of an oblique incision, with the shortest possible length, will allow for the safest procedure possible, thus minimizing the risk of iatrogenic IPBSN injury, and improving patient outcomes and postoperative quality-of-life.

Intersession reliability of the interpolated twitch technique applied during isometric, concentric, and eccentric actions of the human knee extensor muscles.

INTRODUCTION: Although it has been shown that voluntary activation (%VA) of the knee extensors during isometric contractions can be reliably assessed with the interpolated twitch technique, little is known about the reliability of %VA during concentric and eccentric muscle actions. Therefore, relative and absolute intersession reliability of quadriceps muscle's %VA during different contraction modes was determined. METHODS: After a familiarization session, 21 participants (17 males, 25 ± 2 yrs) completed two testing sessions. Paired supramaximal electrical stimuli were administered to the femoral nerve during isometric, concentric, eccentric MVCs, and at rest to assess %VA (stimuli were applied at 70° knee flexion). RESULTS AND DISCUSSION: Data indicate that %VA of the knee extensors can be reliably measured during isometric [intraclass correlation coefficient (ICC) = 0.89, coefficient of variation (CV) = 4.1%], concentric (ICC = 0.87, CV = 6.6%), and eccentric muscle actions (ICC = 0.86, CV = 7.0%). Muscle Nerve 56: 324-327, 2017.

New insights into the potentiation of the first and second phases of the M-wave after voluntary contractions in the quadriceps muscle.

INTRODUCTION: We investigated the mechanisms underlying the potentiation of the first and second phases of the compound action potential (M-wave) after conditioning contractions. METHODS: M-waves were evoked in the knee extensors before and after isometric maximal voluntary contractions (MVCs) of 1 s, 3 s, 6 s, 10 s, 30 s, and 60 s. The amplitude, duration, and area of the M-wave first and second phases were measured during the 10-min period after each contraction. RESULTS: The magnitude of the M-wave first phase was enlarged only after MVCs of 30 s and 60 s, whereas the second phase increased after all MVCs, regardless of their duration. The enlargement of the first phase remained for longer than 2 min, whereas the potentiation of the second phase lasted only 20 s. CONCLUSIONS: Potentiation of the first phase is the result of fatigue-induced membrane changes, whereas enlargement of the second phase is probably related to shortening of muscle fascicles. Muscle Nerve 55: 35-45, 2017.

Imaging Nerve Pathology of the Knee: Magnetic Resonance Imaging and Ultrasound.

Peripheral neuropathies are not uncommon, and the diagnostic evaluation includes a clinical assessment and electrophysiologic studies as well as diagnostic imaging. Magnetic resonance imaging (MRI) and high-resolution ultrasound (HRUS) are of special importance in providing the surgeon with information in the context of nerve trauma, entrapment, and nerve involvement by tumors. Peripheral neuropathy about the knee can occur in the context of associated knee pathology such as trauma, as part of a systemic disease, or as an isolated finding. In this review, we discuss the role of MRI and HRUS in the evaluation of peripheral neuropathy and present imaging examples of peripheral neuropathy involving the knee.

Which imaging method should be used for genicular nerve radio frequency thermocoagulation in chronic knee osteoarthritis?

This study aimed to perform genicular nerve RF neurotomy using two different imaging methods, fluoroscopy and ultrasound, and to compare the clinical effects and reliability of the two methods. Fifty patients with osteoarthritis were included in this study. Patients were randomly allocated into group 1 (fluoroscopy imaging) and group 2 (ultrasound imaging). Outcomes were measured using a pain scale (visual analog scale; VAS) and the Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis. The application time in the ultrasound group (20.2 ± 6.4 min) was shorter than in the fluoroscopy group (25 ± 4.8 min) (p < 0.05). There was no difference in pain relief and functional status between the ultrasound and fluoroscopy groups. Decrease in VAS score and WOMAC total score in the first and third months was significant in both groups (p < 0.001). GNRFT under ultrasound guidance was easily applicable, safe and dynamic, and required no radiation to achieve the same benefit as the fluoroscopy-guided interventions.

Motor Neuron Pools of Synergistic Thigh Muscles Share Most of Their Synaptic Input.

Neural control of synergist muscles is not well understood. Presumably, each muscle in a synergistic group receives some unique neural drive and some drive that is also shared in common with other muscles in the group. In this investigation, we sought to characterize the strength, frequency spectrum, and force dependence of the neural drive to the human vastus lateralis and vastus medialis muscles during the production of isometric knee extension forces at 10 and 30% of maximum voluntary effort. High-density surface electromyography recordings were decomposed into motor unit action potentials to examine the neural drive to each muscle. Motor unit coherence analysis was used to characterize the total neural drive to each muscle and the drive shared between muscles. Using a novel approach based on partial coherence analysis, we were also able to study specifically the neural drive unique to each muscle (not shared). The results showed that the majority of neural drive to the vasti muscles was a cross-muscle drive characterized by a force-dependent strength and bandwidth. Muscle-specific neural drive was at low frequencies (<5 Hz) and relatively weak. Frequencies of neural drive associated with afferent feedback (6-12 Hz) and with descending cortical input (∼20 Hz) were almost entirely shared by the two muscles, whereas low-frequency (<5 Hz) drive comprised shared (primary) and muscle-specific (secondary) components. This study is the first to directly investigate the extent of shared versus independent control of synergist muscles at the motor neuron level. SIGNIFICANCE STATEMENT: Precisely how the nervous system coordinates the activity of synergist muscles is not well understood. One possibility is that muscles of a synergy share a common neural drive. In this study, we directly compared the relative strength of shared versus independent neural drive to synergistically activated thigh muscles in humans. The results of this analysis support the notion that synergistically activated muscles share most of their neural drive. Scientifically, this study addressed an important gap in our current understanding of how neural drive is delivered to synergist muscles. We have also demonstrated the feasibility of a novel approach to the study of muscle synergies based on partial coherence analysis of motor unit activity.

Increasing cutaneous afferent feedback improves proprioceptive accuracy at the knee in patients with sensory ataxia.

Hereditary sensory and autonomic neuropathy type III (HSAN III) features disturbed proprioception and a marked ataxic gait. We recently showed that joint angle matching error at the knee is positively correlated with the degree of ataxia. Using intraneural microelectrodes, we also documented that these patients lack functional muscle spindle afferents but have preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying more on proprioceptive cues provided by tactile afferents. We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape could improve proprioceptive accuracy in patients with a congenital absence of functional muscle spindles. Passive joint angle matching at the knee was used to assess proprioceptive accuracy in 25 patients with HSAN III and 9 age-matched control subjects, with and without taping. Angles of the reference and indicator knees were recorded with digital inclinometers and the absolute error, gradient, and correlation coefficient between the two sides calculated. Patients with HSAN III performed poorly on the joint angle matching test [mean matching error 8.0 ± 0.8° (±SE); controls 3.0 ± 0.3°]. Following application of tape bilaterally to the knee in an X-shaped pattern, proprioceptive performance improved significantly in the patients (mean error 5.4 ± 0.7°) but not in the controls (3.0 ± 0.2°). Across patients, but not controls, significant increases in gradient and correlation coefficient were also apparent following taping. We conclude that taping improves proprioception at the knee in HSAN III, presumably via enhanced sensory feedback from the skin.

Differences in the recruitment curves obtained with monopolar and bipolar electrode configurations in the quadriceps femoris.

INTRODUCTION: We sought to verify whether the stimulation intensity at which M-wave amplitude reaches a plateau actually corresponds to full motor unit activation in monopolar and bipolar configurations. METHODS: M-waves and twitches were evoked using femoral nerve stimulation of gradually increasing intensity in 21 subjects. Recruitment curves corresponding to the amplitude of the first phase (AmpliFIRST ) and peak-to-peak amplitude (AmpliPP ) of the M-wave were obtained in the vastus lateralis, vastus medialis, and rectus femoris in monopolar and bipolar configurations. RESULTS: In all muscles, bipolar M-waves and twitches reached plateau at a significantly lower stimulus intensity compared with monopolar M-waves (P < 0.05). The different behavior of monopolar and bipolar M-waves with stimulus intensity was found for both AmpliFIRST and AmpliPP . CONCLUSIONS: In a bipolar configuration, the stimulus intensity at which M-waves plateau should be increased by at least 10%-20% to achieve complete motor unit recruitment. Muscle Nerve 54: 118-131, 2016.

Is gamma loop dysfunction related to bilateral inhibition in anterior knee pain?

INTRODUCTION: The potential relationship between bilateral quadriceps inhibition in individuals with unilateral anterior knee pain (AKP) and gamma loop dysfunction is examined in this study. METHODS: Twelve individuals with unilateral AKP and 10 healthy controls were recruited. Quadriceps voluntary activation (%VA) was quantified using a triggered interpolated twitch technique. Gamma loop function was assessed through knee extension maximum voluntary isometric contractions before and after 20 minutes of 50-Hz patellar tendon vibration. RESULTS: The AKP group exhibited 5.7% lower %VA bilaterally compared with controls (P = 0.039, Cohen d = 0.79). After prolonged vibration, both groups exhibited an average 8.5% reduction in knee extension force in each limb (P < 0.001, Cohen d = 0.85). CONCLUSIONS: Significant force reductions after vibration suggest that gamma loop dysfunction was not seen in either control or AKP participants. Bilateral quadriceps inhibition in the AKP group does not appear to be associated with gamma loop dysfunction.