Deleterious, protein-altering variants in the transcriptional coregulator ZMYM3 in 27 individuals with a neurodevelopmental delay phenotype.

Neurodevelopmental disorders (NDDs) result from highly penetrant variation in hundreds of different genes, some of which have not yet been identified. Using the MatchMaker Exchange, we assembled a cohort of 27 individuals with rare, protein-altering variation in the transcriptional coregulator ZMYM3, located on the X chromosome. Most (n = 24) individuals were males, 17 of which have a maternally inherited variant; six individuals (4 male, 2 female) harbor de novo variants. Overlapping features included developmental delay, intellectual disability, behavioral abnormalities, and a specific facial gestalt in a subset of males. Variants in almost all individuals (n = 26) are missense, including six that recurrently affect two residues. Four unrelated probands were identified with inherited variation affecting Arg441, a site at which variation has been previously seen in NDD-affected siblings, and two individuals have de novo variation resulting in p.Arg1294Cys (c.3880C>T). All variants affect evolutionarily conserved sites, and most are predicted to damage protein structure or function. ZMYM3 is relatively intolerant to variation in the general population, is widely expressed across human tissues, and encodes a component of the KDM1A-RCOR1 chromatin-modifying complex. ChIP-seq experiments on one variant, p.Arg1274Trp, indicate dramatically reduced genomic occupancy, supporting a hypomorphic effect. While we are unable to perform statistical evaluations to definitively support a causative role for variation in ZMYM3, the totality of the evidence, including 27 affected individuals, recurrent variation at two codons, overlapping phenotypic features, protein-modeling data, evolutionary constraint, and experimentally confirmed functional effects strongly support ZMYM3 as an NDD-associated gene.

MRI Assessment of Sacroiliitis With High-Resolution Protocol.

Background: Sacroiliac (SI) joint subchondral resorption on high-resolution magnetic resonance imaging (MRI) may be an early sign of the development of sacroiliitis. At our institution, high-resolution intermediate-weighted (proton density) MRI sequences are used in the workup of suspected spondyloarthritis (SpA). Questions/Purpose: We sought to test the hypothesis that SI joint subchondral resorption might be a useful MRI feature in the diagnosis of sacroiliitis. Methods: We retrospectively reviewed the records of patients with suspected SpA from a single rheumatologist's practice from January 1, 2010, to December 31, 2017. Patients had an MRI of the SI joints, using our institution's specialized protocol, and underwent standard physical examination and laboratory evaluation. The sensitivity and specificity of SI joint subchondral resorption in the identification of sacroiliitis were estimated using the clinical diagnosis as the reference standard and from a Bayesian latent class model with conditional dependence. Results: SI joint subchondral resorption on SI joint MRI was highly correlated with a positive diagnosis in patients worked up for axial SpA. It demonstrated superior sensitivity when compared with other MRI features used in the MRI diagnosis of sacroiliitis, such as bone marrow edema pattern, erosion, and ankylosis. Interobserver reliability was high for subchondral resorption. Conclusion: This retrospective study found that subchondral resorption on MRI evaluation of the SI joints appeared to be a sensitive indicator of SpA, potentially of early disease. This imaging feature warrants evaluation in other cohorts of patients suspected of having axial SpA to validate diagnostic performance in diverse populations.

What is the Diagnostic Accuracy of MRI for Component Loosening in THA?

BACKGROUND: Implant loosening is a common cause of reoperation after THA. Plain radiographs have been the default modality to evaluate loosening, although radiographs provide a relatively insensitive assessment of integration; cross-sectional modalities may provide a more detailed evaluation but traditionally have suffered from metal-related artifacts. We sought to determine whether MRI is capable of reliably detecting operatively confirmed component loosening in patients after hip arthroplasty. QUESTIONS/PURPOSES: (1) Is assessing implant integration using MRI (with multiacquisition variable resonance image combination, [MAVRIC]) repeatable between readers? (2) What is the sensitivity and specificity of MRI with MAVRIC to evaluate component loosening, using intraoperative assessment as a gold standard? (3) How does the sensitivity and specificity of MRI with MAVRIC for surgically confirmed component loosening compare with those of radiographs? METHODS: Between 2012 and 2017, 2582 THAs underwent revision at one institution. Of those, 219 had a preoperative MRI with MAVRIC. During that period, the most common indication for obtaining an MRI was evaluation of potential adverse local tissue reaction. The surgeons' decision to proceed with revision was based on their overall assessment of clinical, imaging, and laboratory findings, with MRI findings cited as contributing to the decision to revise commonly occurring in the setting of recalled implants. Of the THAs that underwent MRI, 212 were included in this study, while seven were excluded due to equivocal operative notes (5) and excessively poor quality MRI (2). MRI was performed at 1.5T using a standardized arthroplasty imaging protocol, including MARS (metal artifact reduction sequencing) and MAVRIC techniques. Two independent musculoskeletal fellowship-trained readers (one with 26 and one with 5 years of experience) blinded to operative findings scored a subset of 57 hips for implant integration based on Gruen zone and component loosening (defined as complete circumferential loss of integration around a component) to evaluate interobserver reliability. A third investigator blinded to imaging findings reviewed operative notes for details on the surgeon's assessment of intraoperative loosening. RESULTS: Gwet's agreement coefficients (AC) were used to describe interobserver agreement; these are similar to Cohen's kappa but are more resistant to certain paradoxes, such as unexpectedly low values in the setting of very high or low trait prevalence, or good agreement between readers on marginal counts. Almost perfect interobserver agreement (AC2 = 0.81-1.0) was demonstrated for all acetabular zones and all femoral Gruen zones on MRI, while perfect (AC1 = 1.0) agreement was demonstrated for the overall assessment of acetabular component loosening and near perfect agreement was shown for the assessment of femoral component loosening (AC1 = 0.98). MRI demonstrated a sensitivity and specificity of 83% (95% CI, 65-96) and 98% (95% CI, 97-100), respectively, for acetabular component loosening and 75% (95% CI, 55-94) and 100% (95% CI, 100-100), respectively, for femoral component loosening. Radiographs demonstrated a sensitivity and specificity of 26% (95% CI, 12-47) and 100% (95% CI, 96-100), respectively, for acetabular component loosening and 20% (95% CI, 9-47) and 100% (95% CI, 100-100), respectively, for femoral component loosening. CONCLUSION: MRI may provide a repeatable assessment of implant integration and demonstrated greater sensitivity than radiographs for surgically confirmed implant loosening in patients undergoing revision THA at a single institution. Additional multi-institutional studies may provide more insight into the generalizability of these findings. LEVEL OF EVIDENCE: Level III, diagnostic study.

Pseudoaneurysm after total knee arthroplasty: imaging findings in 7 patients.

OBJECTIVE: To describe the clinical presentation of arterial pseudoaneurysms following total knee arthroplasty (TKA) and their diagnostic imaging features on ultrasound and magnetic resonance angiography (MRA) in 7 patients. MATERIALS AND METHODS: A search of our radiology report database from 2007 to 2017 yielded 7 patients with a pseudoaneurysm diagnosed by imaging after TKA. Clinical notes and imaging were reviewed. RESULTS: All 7 patients were male and ranged in age from 53 to 68 (mean 61) years. All patients presented with a painful swollen knee and hemarthrosis within the first month following surgery. Five patients presented after primary TKA. One patient presented after explantation for septic arthritis and another after partial synovectomy for septic arthritis without explantation. Ultrasound identified the pseudoaneurysm as a hypoechoic or hyperechoic mass with a "yin-yang" appearance of turbulent arterial flow and associated complex joint effusion. On MRA, the pseudoaneurysm was a mass next to a parent artery showing avid contrast enhancement in the arterial phase that persisted into the venous phase and washed out in the late venous phase. Six pseudoaneurysms arose from lateral geniculate arteries and 1 from a medial geniculate artery. There were no popliteal artery pseudoaneurysms. Five patients were treated endovascularly, 1 patient thrombosed without intervention, and 1 patient was treated with open surgery. CONCLUSION: Pseudoaneurysm is a potential source of a painful swollen knee with hemarthrosis or a drop in hematocrit after TKA and can be identified with either ultrasound or MRA.

Advanced MRI Techniques for the Hip Joint: Focus on the Postoperative Hip.

OBJECTIVE: Imaging the hip joint with optimized MRI protocol parameters provides the radiologist with the ability to reliably diagnose complex hip abnormalities. The institution of appropriate metal artifact reduction techniques and dedicated sequences can enhance visualization of the periprosthetic bone and soft tissues and allow improved detection of the more frequently encountered total hip arthroplasty-related conditions, such as mechanical loosening, polyethylene wear, and adverse local tissue reactions. CONCLUSION: Finally, through the use of dynamic contrast-enhanced MRI, abnormal femoral head perfusion, one of the most common complications associated with femoral neck fracture internal fixation, can be detected before the development of femoral head osteonecrosis, subchondral collapse, and secondary osteoarthritis. Thus, through the institution of the techniques described in this review article, the challenges associated with MRI of hip arthroplasty and instrumentation can be overcome, allowing for the diagnosis of common associated complications.

Clues to vascular disorders at non-contrast CT of the chest, abdomen, and pelvis.

Non-contrast chest CT scans are commonly performed while CT scans of the abdomen and pelvis are performed in a select subset of patients; those with limited renal function, an allergy to iodinated contrast, in the setting of suspected renal calculus, retroperitoneal hematoma, common duct calculus, abdominal aortic aneurysm with or without rupture, and in patients undergoing a PET-CT scan. In the absence of intravenous contrast, vascular structures may prove challenging to evaluate, yet their assessment is an important component of every non-contrast CT examination. We describe the key imaging features of both arterial and venous pathology, and review clues and common associated non-vascular findings, which can help the radiologist identify vascular disorders at non-contrast CT. Briefly, alternative imaging options are discussed.

Rupture of the short head component of a bifurcated distal biceps tendon.

BACKGROUND: Rupture of the short head component of a bifurcated distal biceps tendon is a rare injury that may be difficult to diagnose and to treat. METHODS: Three cases of patients with selective disruption of the short head of the biceps distal tendon from a single institution are reported. The presenting history, physical examination, imaging studies, operative findings, and treatment strategies are described. RESULTS: In each case, the mechanism of injury was forceful flexion of the involved elbow against an eccentric load. Notable physical examination findings included a palpable tendon in the antecubital fossa, a "reverse Popeye" deformity, and pain and weakness with resisted forearm supination and elbow flexion. Careful review of the magnetic resonance imaging studies demonstrated the classic findings for this unique injury. All 3 patients successfully returned to their baseline level of activity after anatomic repair of the short head component with or without independent repair of the long head component (depending on the degree of partial tearing seen intraoperatively). DISCUSSION/CONCLUSIONS: Rupture of the short head component of a bifurcated distal biceps tendon is a rare injury that can be easily misdiagnosed and mistreated. A meticulous physical examination and evaluation of imaging is required to differentiate this injury from a partial or complete tear of a common distal biceps tendon. Clinicians should maintain a high index of suspicion for this unusual injury pattern. When it is diagnosed appropriately, selective disruption of the short head of the biceps distal tendon may be effectively treated with anatomic repair.

Imaging of Inflammatory Arthritis in Adults: Status and Perspectives on the Use of Radiographs, Ultrasound, and MRI.

The term inflammatory arthritis encompasses a variety of conditions featuring synovial inflammation as a defining characteristic, with resultant local tissue damage occurring over time. These arthritides often share overlapping clinical and imaging characteristics, although the pattern of joint involvement, specific appearance of pathologic changes, and associated findings often allow imaging-based differentiation or individual arthritides.

Imaging of Musculoskeletal Infection.

Diagnostic imaging plays a crucial role in confirming the diagnosis of musculoskeletal (MSK) infection and determining the severity and extent of disease. The clinical diagnosis may be challenging due to the nonspecific presentation of pain and swelling. There are certain features that are pathognomonic for infection. Pre-existing conditions an make diagnosing infection difficult. Prior surgery can create artifacts on advanced imaging modalities such as computed tomography and MRI, obscuring the tissues immediately around the hardware. Recent technological advances have improved physicians' ability to diagnose MSK infection with greater sensitivity, specificity, and accuracy.