Electrodiagnostic subtyping in Guillain-Barré syndrome patients in the International Guillain-Barré Outcome Study.

BACKGROUND AND PURPOSE: Various electrodiagnostic criteria have been developed in Guillain-Barré syndrome (GBS). Their performance in a broad representation of GBS patients has not been evaluated. Motor conduction data from the International GBS Outcome Study (IGOS) cohort were used to compare two widely used criterion sets and relate these to diagnostic amyotrophic lateral sclerosis criteria. METHODS: From the first 1500 patients in IGOS, nerve conduction studies from 1137 (75.8%) were available for the current study. These patients were classified according to nerve conduction studies criteria proposed by Hadden and Rajabally. RESULTS: Of the 1137 studies, 68.3% (N = 777) were classified identically according to criteria by Hadden and Rajabally: 111 (9.8%) axonal, 366 (32.2%) demyelinating, 195 (17.2%) equivocal, 35 (3.1%) inexcitable and 70 (6.2%) normal. Thus, 360 studies (31.7%) were classified differently. The areas of differences were as follows: 155 studies (13.6%) classified as demyelinating by Hadden and axonal by Rajabally; 122 studies (10.7%) classified as demyelinating by Hadden and equivocal by Rajabally; and 75 studies (6.6%) classified as equivocal by Hadden and axonal by Rajabally. Due to more strictly defined cutoffs fewer patients fulfilled demyelinating criteria by Rajabally than by Hadden, making more patients eligible for axonal or equivocal classification by Rajabally. In 234 (68.6%) axonal studies by Rajabally the revised El Escorial (amyotrophic lateral sclerosis) criteria were fulfilled; in axonal cases by Hadden this was 1.8%. CONCLUSIONS AND DISCUSSION: This study shows that electrodiagnosis in GBS is dependent on the criterion set utilized, both of which are based on expert opinion. Reappraisal of electrodiagnostic subtyping in GBS is warranted.

Functional Anatomy of Urogenital Hiatus Closure: the Perineal Complex Triad Hypothesis.

INTRODUCTION: Urogenital hiatus enlargement is a critical factor associated with prolapse and operative failure. This study of the perineal complex was performed to understand how interactions among its three structures: the levator ani, perineal membrane, and perineal body-united by the vaginal fascia-work to maintain urogenital hiatus closure. METHODS: Magnetic resonance images from 30 healthy nulliparous women with 3D reconstruction of selected subjects were used to establish overall geometry. Connection points and lines of action were based on perineal dissection in 10 female cadavers (aged 22-86 years), cross sections of 4 female cadavers (aged 14-35 years), and histological sections (cadavers aged 16 and 21 years). RESULTS: The perineal membrane originates laterally from the ventral two thirds of the ischiopubic rami and attaches medially to the perineal body and vaginal wall. The levator ani attaches to the perineal membrane's cranial surface, vaginal fascia, and the perineal body. The levator line of action in 3D reconstruction is oriented so that the levator pulls the medial perineal membrane cranio-ventrally. In cadavers, simulated levator contraction and relaxation along this vector changes the length of the membrane and the antero-posterior diameter of the urogenital hiatus. Loss of the connection of the left and right perineal membranes through the perineal body results in diastasis of the levator and a widened hiatus, as well as a downward rotation of the perineal membrane. CONCLUSION: Interconnections involving the levator ani muscles, perineal membrane, perineal body, and vaginal fascia form the perineal complex surrounding the urogenital hiatus in an arrangement that maintains hiatal closure.

Pelvic floor injury during vaginal birth is life-altering and preventable: what can we do about it?

Pelvic floor disorders after childbirth have distressing lifelong consequences for women, requiring more than 300,000 women to have surgery annually. This represents approximately 10% of the 3 million women who give birth vaginally each year. Vaginal birth is the largest modifiable risk factor for prolapse, the pelvic floor disorder most strongly associated with birth, and is an important contributor to stress incontinence. These disorders require 10 times as many operations as anal sphincter injuries. Imaging shows that injuries of the levator ani muscle, perineal body, and membrane occur in up to 19% of primiparous women. During birth, the levator muscle and birth canal tissues must stretch to more than 3 times their original length; it is this overstretching that is responsible for the muscle tear visible on imaging rather than compression or neuropathy. The injury is present in 55% of women with prolapse later in life, with an odds ratio of 7.3, compared with women with normal support. In addition, levator damage can affect other aspects of hiatal closure, such as the perineal body and membrane. These injuries are associated with an enlarged urogenital hiatus, now known as antedate prolapse, and with prolapse surgery failure. Risk factors for levator injury are multifactorial and include forceps delivery, occiput posterior birth, older maternal age, long second stage of labor, and birthweight of >4000 g. Delivery with a vacuum device is associated with reduced levator damage. Other steps that might logically reduce injuries include manual rotation from occiput posterior to occiput anterior, slow gradual delivery, perineal massage or compresses, and early induction of labor, but these require study to document protection. In addition, teaching women to avoid pushing against a contracted levator muscle would likely decrease injury risk by decreasing tension on the vulnerable muscle origin. Providing care for women who have experienced difficult deliveries can be enhanced with early recognition, physical therapy, and attention to recovery. It is only right that women be made aware of these risks during pregnancy. Educating women on the long-term pelvic floor sequelae of childbirth should be performed antenatally so that they can be empowered to make informed decisions about management decisions during labor.

The influence of chair recline and head and neck position on upper trapezius activity and stiffness during seated computer work.

Increasing chair recline during seated computer work may reduce the load placed on the upper trapezius (UT), a common location of pain for those with idiopathic chronic neck pain. This study determined the effect of increasing chair recline on UT stiffness and muscle activity during computer work in people with and without idiopathic chronic neck pain. Surface electromyography and ultrasound shear wave elastography were collected from three subdivisions of the UT in 15 individuals with idiopathic chronic neck pain and 15 sex-matched healthy controls. Participants sat in a standardized computer-work setup while chair recline (0°, 25°, 45°) and head and neck position (self-selected, neutral, flexed) were systematically adjusted and maintained for 2.5-min intervals. Repeated-measures ANOVAs were completed for each sex, muscle, and data type, with group (chronic neck pain, control), chair recline (0°,25°,45°), head and neck position (self-selected, flexed, neutral), and side of collected data (dominant, non-dominant) as fixed factors. Men with idiopathic chronic neck pain demonstrated greater UT stiffness in the cranial subdivision when compared to healthy men. Additionally, the 25° and 45° recline levels increased the stiffness of men's dominant UT compared to men's non-dominant UT. Women's UT was more affected by head and neck position, and a neutral head and neck position resulted in lower UT activation, but higher UT stiffness for the cranial subdivision and midway between C-7 and the acromion process. Overall, our findings suggest that the commonly suggested neutral position may not be a beneficial prompt when positioning someone during seated computer work.

Predicting Leg Forces and Knee Moments Using Inertial Measurement Units: An In Vitro Study.

We compared the ability of seven machine learning algorithms to use wearable inertial measurement unit (IMU) data to identify the severe knee loading cycles known to induce microdamage associated with anterior cruciate ligament rupture. Sixteen cadaveric knee specimens, dissected free of skin and muscle, were mounted in a rig simulating standardized jump landings. One IMU was located above and the other below the knee, the applied three-dimensional action and reaction loads were measured via six-axis load cells, and the three-dimensional knee kinematics were also recorded by a laboratory motion capture system. Machine learning algorithms were used to predict the knee moments and the tibial and femur vertical forces; 13 knees were utilized for training each model, while three were used for testing its accuracy (i.e., normalized root-mean-square error) and reliability (Bland-Altman limits of agreement). The results showed the models predicted force and knee moment values with acceptable levels of error and, although several models exhibited some form of bias, acceptable reliability. Further research will be needed to determine whether these types of models can be modified to attenuate the inevitable in vivo soft tissue motion artifact associated with highly dynamic activities like jump landings.

A unified pelvic floor conceptual model for studying morphological changes with prolapse, age, and parity.

Several 2-dimensional and 3-dimensional measurements have been used to assess changes in pelvic floor structures and shape. These include assessment of urogenital and levator hiatus dimensions, levator injury grade, levator bowl volume, and levator plate shape. We argue that each assessment reflects underlying changes in an individual aspect of the overall changes in muscle and fascial structures. Vaginal delivery, aging, and interindividual variations in anatomy combine to affect pelvic floor structures and their connections in different ways. To date, there is no unifying conceptual model that permits the evaluation of how these many measures relate to one another or that reflects overall pelvic floor structure and function. Therefore, this study aimed to describe a unified pelvic floor conceptual model to better understand how the aforementioned changes to the pelvic floor structures and their biomechanical interactions affect pelvic organ support with vaginal birth, prolapse, and age. In this model, the pelvic floor is composed of 5 key anatomic structures: the (1) pubovisceral, (2) puborectal, and (3) iliococcygeal muscles with their superficial and inferior fascia; (4) the perineal membrane or body; and (5) the anal sphincter complex. Schematically, these structures are considered to originate from pelvic sidewall structures and meet medially at important connection points that include the anal sphincter complex, perineal body, and anococcygeal raphe. The pubovisceral muscle contributes primarily to urogenital hiatus closure, whereas the puborectal muscle is mainly related to levator hiatus closure, although each muscle contributes to the other. Dorsally and laterally, the iliococcygeal muscle forms a shelflike structure in women with normal support that spans the remaining area between these medial muscles and attachments to the pelvic sidewall. Other features include the levator plate, bowl volume, and anorectal angle. The pelvic floor conceptual model integrates existing observations and points out evident knowledge gaps in how parturition, injury, disease, and aging can contribute to changes associated with pelvic floor function caused by the detachment of one or more important connection points or pubovisceral muscle failure.

Relationship Between Lateral Tibial Posterior Slope and Tibiofemoral Kinematics During Simulated Jump Landings in Male Cadaveric Knees.

Background: It is not known mechanistically whether a steeper lateral posterior tibial slope (LTS) leads to an increase in anterior tibial translation (ATT) as well as internal tibial rotation (ITR) during a given jump landing. Hypothesis: A steeper LTS will result in increased ATT and ITR during simulated jump landings when applying knee compression, flexion, and internal tibial torque of increasing severity. Study Design: Descriptive laboratory study. Methods: Seven pairs of cadaveric knees were harvested from young male adult donors (mean ± SD; age, 25.71 ± 5.53 years; weight, 71.51 ± 4.81 kg). The LTS of each knee was measured by a blinded observer from 3-T magnetic resonance images. Two sets of 25 impact trials of ∼700 N (1× body weight [BW] ±10%) followed by 2 sets of 25 trials of 1400 N (2× BW ±10%) were applied to a randomly selected knee of each pair. Similarly, on the contralateral knee, 2 sets of 25 impact trials of ∼1800 N (2.5× BW ±10%) followed by 2 sets of 25 trials of ∼2100 N (3× BW ±10%) were applied. Three-dimensional knee kinematics, including ATT and ITR, were measured at 400 Hz using optoelectronic motion capture. Two-factor linear mixed effect models were used to determine the relationship of LTS to ATT and ITR as impact loading increased. Results: As LTS increased, so did ATT and ITR during increasingly severe landings. LTS had an increasing effect on ATT (coefficient, 0.50; 95% CI, 0.29-0.71) relative to impact force (coefficient, 0.52; 95% CI, 0.50-0.53). ITR was proportional to LTS (coefficient, 1.36; 95% CI, 0.80-1.93) under increasing impact force (coefficient, 0.49; 95% CI, 0.47-0.52). For steeper LTS, the increase in ITR was proportionally greater than the increase in ATT. Conclusion: In male knee specimens, a steeper LTS significantly increased ATT and ITR during jump landings. Clinical Relevance: Increases in ITR and ATT during jump landings lead to increased strain on the anterior cruciate ligament and are therefore associated with greater risk of ligament failure.

Fatigue-driven compliance increase and collagen unravelling in mechanically tested anterior cruciate ligament.

Approximately 300,000 anterior cruciate ligament (ACL) tears occur annually in the United States, half of which lead to the onset of knee osteoarthritis within 10 years of injury. Repetitive loading is known to result in fatigue damage of both ligament and tendon in the form of collagen unravelling, which can lead to structural failure. However, the relationship between tissue's structural, compositional, and mechanical changes are poorly understood. Herein we show that repetitive submaximal loading of cadaver knees causes an increase in co-localised induction of collagen unravelling and tissue compliance, especially in regions of greater mineralisation at the ACL femoral enthesis. Upon 100 cycles of 4× bodyweight knee loading, the ACL exhibited greater unravelled collagen in highly mineralized regions across varying levels of stiffness domains as compared to unloaded controls. A decrease in the total area of the most rigid domain, and an increase in the total area of the most compliant domain was also found. The results highlight fatigue-driven changes in both protein structure and mechanics in the more mineralized regions of the ACL enthesis, a known site of clinical ACL failure. The results provide a starting point for designing studies to limit ligament overuse injury.

Levels of ACL-straining activities increased in the six months prior to non-contact ACL injury in a retrospective survey: evidence consistent with ACL fatigue failure.

Introduction: Recent evidence has emerged suggesting that a non-contact anterior cruciate ligament (ACL) tear can result from repetitive submaximal loading of the ligament. In other words, when the intensity of ACL-straining athletic activities is increased too rapidly, microdamage can accumulate in the ligament beyond the rate at which it can be repaired, thereby leading to material fatigue in the ligament and its eventual failure. The objective of this survey-based exploratory study was to retrospectively determine whether the levels of various athletic activities performed by ACL-injured patients significantly changed during the 6 months before injury. Methods: Forty-eight ACL-injured patients completed a survey to characterize their participation in various activities (weightlifting, sport-specific drills, running, jumping, cutting, pivoting/twisting, and decelerating) at three timepoints (1 week, 3 months, 6 months) prior to ACL injury. Activity scores, which summarized the frequency and intensity of each activity, were calculated for each patient at each time interval. A series of linear mixed-effects regression models was used to test whether there was a significant change in levels of the various activities in the 6-month period leading up to ACL injury. Results: Patients who sustained a non-contact ACL injury markedly increased their sport-specific drills activity levels in the time leading up to injury (p = 0.098), while those patients who sustained a contact ACL injury exhibited no change in this activity during the same time period (p = 0.829). Levels of running, jumping, cutting, pivoting/twisting, and decelerating increased for non-contact ACL-injured patients but decreased for contact ACL-injured patients, though not significantly (p values > 0.10). Weightlifting activity significantly decreased leading up to injury among contact ACL-injured patients (p = 0.002). Discussion: We conclude that levels of ACL-straining athletic activities or maneuvers in non-contact ACL-injured patients markedly increased in the 6 months leading up to their injury, providing evidence that changing levels of certain activities or maneuvers may play a role in ACL injury risk. This warrants further investigation of the hypothesis that too rapid an increase in activities or maneuvers known to place large loads on the ACL can cause microdamage to accumulate in the ligament, thereby leading to failure.

An Adolescent Murine In Vivo Anterior Cruciate Ligament Overuse Injury Model.

BACKGROUND: Overuse ligament and tendon injuries are prevalent among recreational and competitive adolescent athletes. In vitro studies of the ligament and tendon suggest that mechanical overuse musculoskeletal injuries begin with collagen triple-helix unraveling, leading to collagen laxity and matrix damage. However, there are little in vivo data concerning this mechanism or the physiomechanical response to collagen disruption, particularly regarding the anterior cruciate ligament (ACL). PURPOSE: To develop and validate a novel in vivo animal model for investigating the physiomechanical response to ACL collagen matrix damage accumulation and propagation in the ACL midsubstance, fibrocartilaginous entheses, and subchondral bone. STUDY DESIGN: Controlled laboratory study. METHODS: C57BL/6J adolescent inbred mice underwent 3 moderate to strenuous ACL fatigue loading sessions with a 72-hour recovery between sessions. Before each session, randomly selected subsets of mice (n = 12) were euthanized for quantifying collagen matrix damage (percent collagen unraveling) and ACL mechanics (strength and stiffness). This enabled the quasi-longitudinal assessment of collagen matrix damage accrual and whole tissue mechanical property changes across fatigue sessions. Additionally, all cyclic loading data were quantified to evaluate changes in knee mechanics (stiffness and hysteresis) across fatigue sessions. RESULTS: Moderate to strenuous fatigue loading across 3 sessions led to a 24% weaker (P = .07) and 35% less stiff (P < .01) ACL compared with nonloaded controls. The unraveled collagen densities within the fatigued ACL and entheseal matrices after the second and third sessions were 38% (P < .01) and 15% (P = .02) higher compared with the nonloaded controls. CONCLUSION: This study confirmed the hypothesis that in vivo ACL collagen matrix damage increases with tissue fatigue sessions, adversely impacting ACL mechanical properties. Moreover, the in vivo ACL findings were consistent with in vitro overloading research in humans. CLINICAL RELEVANCE: The outcomes from this study support the use of this model for investigating ACL overuse injuries.

CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome.

BACKGROUND AND OBJECTIVES: To investigate CSF findings in relation to clinical and electrodiagnostic subtypes, severity, and outcome of Guillain-Barré syndrome (GBS) based on 1,500 patients in the International GBS Outcome Study. METHODS: Albuminocytologic dissociation (ACD) was defined as an increased protein level (>0.45 g/L) in the absence of elevated white cell count (<50 cells/µL). We excluded 124 (8%) patients because of other diagnoses, protocol violation, or insufficient data. The CSF was examined in 1,231 patients (89%). RESULTS: In 846 (70%) patients, CSF examination showed ACD, which increased with time from weakness onset: ≤4 days 57%, >4 days 84%. High CSF protein levels were associated with a demyelinating subtype, proximal or global muscle weakness, and a reduced likelihood of being able to run at week 2 (odds ratio [OR] 0.42, 95% CI 0.25-0.70; p = 0.001) and week 4 (OR 0.44, 95% CI 0.27-0.72; p = 0.001). Patients with the Miller Fisher syndrome, distal predominant weakness, and normal or equivocal nerve conduction studies were more likely to have lower CSF protein levels. CSF cell count was <5 cells/µL in 1,005 patients (83%), 5-49 cells/µL in 200 patients (16%), and ≥50 cells/µL in 13 patients (1%). DISCUSSION: ACD is a common finding in GBS, but normal protein levels do not exclude this diagnosis. High CSF protein level is associated with an early severe disease course and a demyelinating subtype. Elevated CSF cell count, rarely ≥50 cells/µL, is compatible with GBS after a thorough exclusion of alternative diagnoses. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that CSF ACD (defined by the Brighton Collaboration) is common in patients with GBS.

Two emerging phenotypes of atypical inclusion body myositis: illustrative cases.

OBJECTIVES: Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in those aged above 50. It is classically heralded by weakness in the long finger flexors and quadriceps. The aim of this article is to describe five atypical cases of IBM, outlining two potential emerging clinical subsets of the disease. METHODS: We reviewed relevant clinical documentation and pertinent investigations for five patients with IBM. RESULTS: The first phenotype we describe is young-onset IBM in two patients who had symptoms since their early thirties. The literature supports that IBM can rarely present in this age range or younger. We describe a second phenotype in three middle-aged women who developed early bilateral facial weakness at presentation in tandem with dysphagia and bulbar impairment followed by respiratory failure requiring non-invasive ventilation (NIV). Within this group, two patients were noted to have macroglossia, another possible rare feature of IBM. CONCLUSIONS: Despite the classical phenotype described within the literature IBM can present in a heterogenous fashion. It is important to recognise IBM in younger patients and investigate for specific associations. The described pattern of facial diplegia, severe dysphagia, bulbar dysfunction and respiratory failure in female IBM patients requires further characterisation. Patients with this clinical pattern may require more complex and supportive management. Macroglossia is a potentially under recognised feature of IBM. The presence of macroglossia in IBM warrants further study, as its presence may lead to unnecessary investigations and delay diagnosis.

Electrochemical Sensing of Urinary Chloride Ion Concentration for Near Real-Time Monitoring.

Urinary chloride concentration is a valuable health metric that can aid in the early detection of serious conditions, such as acid base disorders, acute heart failure, and incidences of acute renal failure in the intensive care unit. Physiologically, urinary chloride levels frequently change and are difficult to measure, involving time-consuming and inconvenient lab testing. Thus, near real-time simple sensors are needed to quickly provide actionable data to inform diagnostic and treatment decisions that affect health outcomes. Here, we introduce a chronopotentiometric sensor that utilizes commercially available screen-printed electrodes to accurately quantify clinically relevant chloride concentrations (5-250 mM) in seconds, with no added reagents or electrode surface modification. Initially, the sensor's performance was optimized through the proper selection of current density at a specific chloride concentration, using electrical response data in conjunction with scanning electron microscopy. We developed a unique swept current density algorithm to resolve the entire clinically relevant chloride concentration range, and the chloride sensors can be reliably reused for chloride concentrations less than 50 mM. Lastly, we explored the impact of pH, temperature, conductivity, and additional ions (i.e., artificial urine) on the sensor signal, in order to determine sensor feasibility in complex biological samples. This study provides a path for further development of a portable, near real-time sensor for the quantification of urinary chloride.

Loading mechanisms of the anterior cruciate ligament.

This review identifies the three-dimensional knee loads that have the highest risk of injuring the anterior cruciate ligament (ACL) in the athlete. It is the combination of the muscular resistance to a large knee flexion moment, an external reaction force generating knee compression, an internal tibial torque, and a knee abduction moment during a single-leg athletic manoeuvre such as landing from a jump, abruptly changing direction, or rapidly decelerating that results in the greatest ACL loads. While there is consensus that an anterior tibial shear force is the primary ACL loading mechanism, controversy exists regarding the secondary order of importance of transverse-plane and frontal-plane loading in ACL injury scenarios. Large knee compression forces combined with a posteriorly and inferiorly sloped tibial plateau, especially the lateral plateau-an important ACL injury risk factor-causes anterior tibial translation and internal tibial rotation, which increases ACL loading. Furthermore, while the ACL can fail under a single supramaximal loading cycle, recent evidence shows that it can also fail following repeated submaximal loading cycles due to microdamage accumulating in the ligament with each cycle. This challenges the existing dogma that non-contact ACL injuries are predominantly due to a single manoeuvre that catastrophically overloads the ACL.

Comparison of in vivo visco-hyperelastic properties of uterine suspensory tissue in women with and without pelvic organ prolapse.

The uterine suspensory tissue (UST) complex includes the cardinal (CL) and uterosacral "ligaments" (USL), which are mesentery-like structures that play a role in resisting pelvic organ prolapse (POP). Since there is no information on the time-dependent material properties of the whole structure in situ and in vivo, we developed and tested an intraoperative technique to quantify in vivo whether there is a significant difference in visco-hyperelastic behavior of the CL and USL between women with and without POP. Thirteen women with POP (cases) and four controls scheduled for surgery were selected from an ongoing POP study. Immediately prior to surgery, a computer-controlled linear servo-actuator with a series force transducer applied a continuous, caudally directed traction force while simultaneously recording the resulting cervical displacement in the same direction. After applying an initial 1.1 N preload, a ramp rate of 4 mm/s was used to apply a maximum force of 17.8 N in three "ramp-and-hold" test trials. A simplified bilateral four-cable biomechanical model was used to identify the material behavior of each ligament. For this, the initial cross-section areas of the CL and USL were measured on 3-T magnetic resonance image-based 3D models from each subject. The time-dependent strain energy function of CL/USL was defined with a three-parameter hyperelastic Mooney-Rivlin material model and a two-term Prony series in relaxation form. When cases were compared with controls, the estimated time-dependent material constants of CL and USL did not differ significantly. These are the first measurements that compare the in vivo and in situ visco-hyperelastic response of the tissues comprising the CL and USL to loading in women with and without prolapse. Larger sample sizes would help improve the precision of intergroup differences.

Hiatal failure: effects of pregnancy, delivery, and pelvic floor disorders on level III factors.

INTRODUCTION AND HYPOTHESIS: The failure of the levator hiatus (LH) and urogenital hiatus (UGH) to remain closed is not only associated with pelvic floor disorders, but also contributes to recurrence after surgical repair. Pregnancy and vaginal birth are key events affecting this closure. An understanding of normal and failed hiatal closure is necessary to understand, manage, and prevent pelvic floor disorders. METHODS: This narrative review was conducted by applying the keywords "levator hiatus" OR "genital hiatus" OR "urogenital hiatus" in PubMed. Articles that reported hiatal size related to pelvic floor disorders and pregnancy were chosen. Weighted averages for hiatal size were calculated for each clinical situation. RESULTS: Women with prolapse have a 22% and 30% larger LH area measured by ultrasound at rest and during Valsalva than parous women with normal support. Women with persistently enlarged UGH have 2-3 times higher postoperative failure rates after surgery for prolapse. During pregnancy, the LH area at Valsalva increases by 29% from the first to the third trimester in preparation for childbirth. The enlarged postpartum hiatus recovers over time, but does not return to nulliparous size after vaginal birth. Levator muscle injury during vaginal birth, especially forceps-assisted, is associated with increases in hiatal size; however, it only explains a portion of hiatus variation-the rest can be explained by pelvic muscle function and possibly injury to other level III structures. CONCLUSIONS: Failed hiatal closure is strongly related to pelvic floor disorders. Vaginal birth and levator injury are primary factors affecting this important mechanism.

An International Perspective on Preceding Infections in Guillain-Barré Syndrome: The IGOS-1000 Cohort.

BACKGROUND AND OBJECTIVES: Infections play a key role in the development of Guillain-Barré syndrome (GBS) and have been associated with specific clinical features and disease severity. The clinical variation of GBS across geographical regions has been suggested to be related to differences in the distribution of preceding infections, but this has not been studied on a large scale. METHODS: We analyzed the first 1,000 patients included in the International GBS Outcome Study with available biosamples (n = 768) for the presence of a recent infection with Campylobacter jejuni, hepatitis E virus, Mycoplasma pneumoniae, cytomegalovirus, and Epstein-Barr virus. RESULTS: Serologic evidence of a recent infection with C. jejuni was found in 228 (30%), M. pneumoniae in 77 (10%), hepatitis E virus in 23 (3%), cytomegalovirus in 30 (4%), and Epstein-Barr virus in 7 (1%) patients. Evidence of more than 1 recent infection was found in 49 (6%) of these patients. Symptoms of antecedent infections were reported in 556 patients (72%), and this proportion did not significantly differ between those testing positive or negative for a recent infection. The proportions of infections were similar across continents. The sensorimotor variant and the demyelinating electrophysiologic subtype were most frequent across all infection groups, although proportions were significantly higher in patients with a cytomegalovirus and significantly lower in those with a C. jejuni infection. C. jejuni-positive patients were more severely affected, indicated by a lower Medical Research Council sum score at nadir (p = 0.004) and a longer time to regain the ability to walk independently (p = 0.005). The pure motor variant and axonal electrophysiologic subtype were more frequent in Asian compared with American or European C. jejuni-positive patients (p < 0.001, resp. p = 0.001). Time to nadir was longer in the cytomegalovirus-positive patients (p = 0.004). DISCUSSION: Across geographical regions, the distribution of infections was similar, but the association between infection and clinical phenotype differed. A mismatch between symptom reporting and serologic results and the high frequency of coinfections demonstrate the importance of broad serologic testing in identifying the most likely infectious trigger. The association between infections and outcome indicates their value for future prognostic models.