Disruption of the Atrophy-based Functional Network in Multiple Sclerosis Is Associated with Clinical Disability: Validation of a Meta-Analytic Model in Resting-State Functional MRI.

Background In multiple sclerosis (MS), gray matter (GM) atrophy exhibits a specific pattern, which correlates strongly with clinical disability. However, the mechanism of regional specificity in GM atrophy remains largely unknown. Recently, the network degeneration hypothesis (NDH) was quantitatively defined (using coordinate-based meta-analysis) as the atrophy-based functional network (AFN) model, which posits that localized GM atrophy in MS is mediated by functional networks. Purpose To test the NDH in MS in a data-driven manner using the AFN model to direct analyses in an independent test sample. Materials and Methods Model fit testing was conducted with structural equation modeling, which is based on the computation of semipartial correlations. Model verification was performed in coordinate-based data of healthy control participants from the BrainMap database (https://www.brainmap.org). Model validation was conducted in prospectively acquired resting-state functional MRI in participants with relapsing-remitting MS who were recruited between September 2018 and January 2019. Correlation analyses of model fit indices and volumetric measures with Expanded Disability Status Scale (EDSS) scores and disease duration were performed. Results Model verification of healthy control participants included 80 194 coordinates from 9035 experiments. Model verification in healthy control data resulted in excellent model fit (root mean square error of approximation, 0.037; 90% CI: 0.036, 0.039). Twenty participants (mean age, 36 years ± 9 [standard deviation]; 12 women) with relapsing-remitting MS were evaluated. Model validation in resting-state functional MRI in participants with MS resulted in deviation from optimal model fit (root mean square error of approximation, 0.071; 90% CI: 0.070, 0.072), which correlated with EDSS scores (r = 0.68; P = .002). Conclusion The atrophy-based functional network model predicts functional network disruption in multiple sclerosis (MS), thereby supporting the network degeneration hypothesis. On resting-state functional MRI scans, reduced functional network integrity in participants with MS had a strong positive correlation with clinical disability. © RSNA, 2021 Online supplemental material is available for this article.

Characterization of normal-appearing white matter in multiple sclerosis using quantitative susceptibility mapping in conjunction with diffusion tensor imaging.

PURPOSE: Quantitative susceptibility mapping (QSM) is influenced by iron as well as myelin, which makes interpretation of pathologic changes challenging. Concurrent acquisition of MR sequences that are sensitive to axonal/myelin integrity, such as diffusion tensor imaging (DTI), may provide context for interpreting quantitative susceptibility (QS) signal. The purpose of our study was to investigate alterations in normal-appearing white matter (NAWM) in multiple sclerosis (MS) using QSM in conjunction with DTI. METHODS: Twenty relapsing-remitting MS patients and 20 age-matched healthy controls (HC) were recruited for this prospective study. QS, radial diffusivity (RD), fractional anisotropy (FA), and R2* maps within the whole brain as well as individual tracts were generated for comparison between NAWM and HC white matter (HCWM). RESULTS: MS lesions demonstrated significant differences in QS, FA, RD, and R2* compared to HCWM (p < 0.03). These metrics did not show a significant difference between whole-brain NAWM and HCWM. Among NAWM tracts, the cingulate gyri demonstrated significantly decreased QS compared to HCWM (p = 0.004). The forceps major showed significant differences in FA and RD without corresponding changes in QS (p < 0.01). CONCLUSION: We found discordant changes in QSM and DTI metrics within the cingulate gyri and forceps major. This may potentially reflect the influence of paramagnetic substrates such as iron, which could be decreased along these NAWM tracts. Our results point to the potential role of QSM as a unique biomarker, although additional validation studies are needed.

Biomechanical properties of suprapectoral biceps tenodesis: double knotless screw fixation is superior to single knotless screw fixation.

INTRODUCTION: The purpose of this study is to biomechanically evaluate a new technique of double knotless screw fixation for suprapectoral biceps tenodesis and compare the results with that of the single knotless screw fixation as well as the interference screw fixation. METHODS: 24 fresh-frozen human cadaveric shoulders with a mean age of 68.3 ± 9 years were studied. The specimens were randomly divided into three experimental biceps tenodesis groups (n = 8): single knotless screw, double knotless screw and interference screw. Each tenodesis specimen was mounted on a mechanical testing machine, preloaded for 2 min at 5 N, tested with cyclic loading from 5 to 70 N for 500 load cycles and subjected to an axial load to failure test (1 mm/s). The ultimate failure load, stiffness, cyclic displacement and mode of failure were evaluated. RESULTS: The interference screw fixation had the highest ultimate failure load (215.8 ± 43.1 N) and stiffness (25.7 ± 5.2 N/mm) which were significantly higher than the corresponding results for the single and double knotless screw groups (P = 0.0029). The double knotless screw group had the second highest ultimate failure load (162.8 ± 13.8 N) and stiffness (15.1 ± 4.1 N/mm) which were significantly higher than the corresponding results for the single knotless screw technique (P = 0.0002). The most common mode of failure was suture slippage for both the double (7/8) and single knotless screw (6/8) groups while biceps tendon tearing occurred most often for the interference screw group (6/8). CONCLUSION: In this biomechanical study, the double knotless screw fixation was found to have a significantly greater ultimate failure load and stiffness than the single knotless screw fixation but lower values than the interference screw fixation.

Biomechanical Comparison of All-Suture Anchor Fixation and Interference Screw Technique for Subpectoral Biceps Tenodesis.

PURPOSE: To compare the biomechanical characteristics of the subpectoral Y-knot all-suture anchor fixation with those of the interference screw technique. METHODS: Sixteen fresh-frozen human cadaveric shoulders with a mean age of 67.6 ± 5.8 years (range, 52 to 74 years) were studied. The specimens were randomly grouped into 2 experimental biceps tenodesis groups (n = 8): Y-knot all-suture anchor or interference screw. The specimens were cyclically tested to failure by applying tensile forces parallel to the longitudinal axis of the humerus. A preload of 5 N was applied for 2 minutes prior to cyclic loading for 500 cycles from 5 to 70 N at 1 Hz; subsequently, a load-to-failure test at 1 mm/s was performed. The ultimate failure load, stiffness, displacement at cyclic and failure loading, and mode of failure were recorded. RESULTS: The all-suture anchor technique displayed values of ultimate failure load and stiffness comparable to that of the interference screw technique. The displacement at cyclic and failure loading of the all-suture anchor trials were significantly greater than the interference screw (P = .0002). The all-suture anchor specimens experienced anchor pullout and tendon tear equally during the trials, whereas the interference screw group experienced tendon tear in most of the cases and screw pullout in 2 trials. CONCLUSIONS: The Y-knot all-suture anchor fixation provides equivalent ultimate failure load and stiffness when compared with the interference screw technique in tenodesis of the proximal biceps tendon from a subpectoral approach. However, the interference screw technique demonstrates significantly less displacement in response to cyclic and failure loading. CLINICAL RELEVANCE: The all-suture anchor fixation is an alternative technique for subpectoral biceps tenodesis even at greater displacement when compared with the interference screw fixation during cyclic and failure loading.

The effect of coracoacromial ligament excision and acromioplasty on the amount of rotator cuff force production necessary to restore intact glenohumeral biomechanics.

HYPOTHESIS AND BACKGROUND: Coracoacromial ligament (CAL) excision and acromioplasty increase superior and anterosuperior glenohumeral translation. It is unknown how much of an increase in rotator cuff force production is required to re-establish intact glenohumeral biomechanics after these surgical procedures. We hypothesized that, after CAL excision and acromioplasty, an increase in rotator cuff force production would not be necessary to reproduce the anterosuperior and superior translations of the intact specimens. METHODS: Nine cadaveric shoulders were subjected to loading in the superior and anterosuperior directions in the intact state after CAL excision, acromioplasty, and recording of the translations. The rotator cuff force was then increased to normalize glenohumeral biomechanics. RESULTS: After CAL excision at 150 and 200 N of loading, an increase in the rotator cuff force by 25% decreased anterosuperior translation to the point where there was no significant difference from the intact specimen's translation. After acromioplasty (and CAL excision) at 150 and 200 N, an increase in the rotator cuff force of 25% and 30%, respectively, decreased superior translation to the point where there was no significant difference from the intact specimen's translation. CONCLUSIONS: At 150 to 200 N of loading, CAL excision and acromioplasty increase the rotator cuff force required to maintain normal glenohumeral biomechanics by 25% to 30%. CLINICAL RELEVANCE: After a subacromial decompression, the rotator cuff has an increased force production requirement to maintain baseline glenohumeral mechanics. Under many circumstances, in vivo force requirements may be even greater after surgical attenuation of the coracoacromial arch. LEVEL OF EVIDENCE: Basic Science Study; Biomechanics.

Long-Term Neurocognitive Outcomes in Pediatric Nonfatal Drowning: Results of a Family Caregiver Survey.

BACKGROUND: Drowning is a leading cause of brain injury in children. Long-term outcome data for drowning survivors are sparse. This study reports neurocognitive outcomes for 154 children hospitalized following drowning. METHODS: A survey for parent caregivers was distributed online. Likert scale items assessed 10 outcome variables in four domains: motor (three), perception (three), language (three), and social/emotional (one). Cluster analysis, outcome relative risk, and descriptive statistics were applied. RESULTS: Of 208 surveys received, 154 met inclusion criteria. Coma was the most common admission status (n = 137). Cluster analysis identified three outcome groups: Mild (n = 39), Moderate (n = 75), and Severe (n = 40). Motor impairment with cognitive and perceptual sparing (deefferentation) was present in Moderate (P < 1 × 10-26) and Severe (P < 1 × 10-12) but absent in Mild. Locked-in state was endorsed in both Moderate (83%) and Severe (70%). The strongest predictor of good outcome (Mild) was hospitalization with no medical intervention (relative risk [RR] = 6.7). Responsivity on admission (RR = 4.2) or discharge (RR = 12.22) also predicted good outcome. In-hospital prognostication and counseling predicted outcome weakly (RR = 1.3) or not at all. CONCLUSIONS: Long-term outcomes in pediatric drowning ranged widely. Overall, motor impairments exceeded perceptual or cognitive (P < 1 × 10-18), with "locked-in state" endorsed in most (93 of 154). The strongest predictors of good outcome were the lack of necessity for interventions and responsivity on admission or discharge. The eponym "Conrad syndrome" is proposed for locked-in state following nonfatal drowning in children.

Intrinsic and extrinsic contributors to subregional thalamic volume loss in multiple sclerosis.

OBJECTIVE: To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo high-gradient diffusion MRI. METHODS: In this cross-sectional study, 41 people with multiple sclerosis and 34 age and sex-matched healthy controls underwent 3T MRI with up to 300 mT/m gradients using a multi-shell diffusion protocol consisting of eight b-values and diffusion time of 19 ms. Each thalamus was parcellated into 25 subregions for volume determination and diffusion metric estimation. The soma and neurite density imaging model was applied to obtain estimates of intra-neurite, intra-soma, and extra-cellular signal fractions for each subregion and within structurally connected white matter trajectories and cortex. RESULTS: Multiple sclerosis-related volume loss was more pronounced in posterior/medial subregions than anterior/ventral subregions. Intra-soma signal fraction was lower in multiple sclerosis, reflecting reduced cell body density, while the extra-cellular signal fraction was higher, reflecting greater extra-cellular space, both of which were observed more in posterior/medial subregions than anterior/ventral subregions. Lower intra-neurite signal fraction in connected normal-appearing white matter and lower intra-soma signal fraction of structurally connected cortex were associated with reduced subregional thalamic volumes. Intrinsic and extrinsic microstructural measures independently related to subregional volume with heterogeneity across atrophy-prone thalamic nuclei. Extrinsic microstructural alterations predicted left anteroventral, intrinsic microstructural alterations predicted bilateral medial pulvinar, and both intrinsic and extrinsic factors predicted lateral geniculate and medial mediodorsal volumes. INTERPRETATION: Our results might be reflective of the involvement of anterograde and retrograde degeneration from white matter demyelination and cerebrospinal fluid-mediated damage in subregional thalamic volume loss.

Detection of grey matter microstructural substrates of neurodegeneration in multiple sclerosis.

Multiple sclerosis features complex pathological changes in grey matter that begin early and eventually lead to diffuse atrophy. Novel approaches to image grey-matter microstructural alterations in vivo are highly sought after and would enable more sensitive monitoring of disease activity and progression. This cross-sectional study aimed to assess the sensitivity of high-gradient diffusion MRI for microstructural tissue damage in cortical and deep grey matter in people with multiple sclerosis and test the hypothesis that reduced cortical cell body density is associated with cortical and deep grey-matter volume loss. Forty-one people with multiple sclerosis (age 24-72, 14 females) and 37 age- and sex-matched healthy controls were scanned on a 3 T Connectom MRI scanner equipped with 300 mT/m gradients using a multi-shell diffusion MRI protocol. The soma and neurite density imaging model was fitted to high-gradient diffusion MRI data to obtain estimates of intra-neurite, intra-cellular and extra-cellular signal fractions and apparent soma radius. Cortical and deep grey-matter microstructural imaging metrics were compared between multiple sclerosis and healthy controls and correlated with grey-matter volume, clinical disability and cognitive outcomes. People with multiple sclerosis showed significant cortical and deep grey-matter volume loss compared with healthy controls. People with multiple sclerosis showed trends towards lower cortical intra-cellular signal fraction and significantly lower intra-cellular and higher extra-cellular signal fractions in deep grey matter, especially the thalamus and caudate, compared with healthy controls. Changes were most pronounced in progressive disease and correlated with the Expanded Disability Status Scale, but not the Symbol Digit Modalities Test. In multiple sclerosis, normalized thalamic volume was associated with thalamic microstructural imaging metrics. Whereas thalamic volume loss did not correlate with cortical volume loss, cortical microstructural imaging metrics were significantly associated with thalamic volume, and not with cortical volume. Compared with the short diffusion time (Δ = 19 ms) achievable on the Connectom scanner, at the longer diffusion time of Δ = 49 ms attainable on clinical scanners, multiple sclerosis-related changes in imaging metrics were generally less apparent with lower effect sizes in cortical and deep grey matter. Soma and neurite density imaging metrics obtained from high-gradient diffusion MRI data provide detailed grey-matter characterization beyond cortical and thalamic volumes and distinguish multiple sclerosis-related microstructural pathology from healthy controls. Cortical cell body density correlates with thalamic volume, appears sensitive to the microstructural substrate of neurodegeneration and reflects disability status in people with multiple sclerosis, becoming more pronounced as disability worsens.

Comparison of changes in shoulder functions between biceps tenotomy and tenodesis in an animal model.

OBJECTIVES: Tenotomy and tenodesis of the long head of biceps tendon are effective pain-relieving treatments. However, there is no consensus on the functional outcome after these surgical procedures. We hypothesized that there would be no difference in ambulation parameters after recovery from the surgery between rats that underwent tenotomy versus tenodesis procedures. METHODS: Twenty-four New Zealand rats were used and randomly divided into three groups. Each group received one of the following surgeries: tenotomy, tenodesis, and sham operation. A video-based walking track system was applied for gait analysis at day -1, 1, 3, 5, 7, 14 and 21 for each rat. Temporal and spatial parameters were obtained, and asymmetric index was calculated for each parameter. RESULTS: Compared to the tenotomy and sham-operated groups, the rats in the tenodesis group had shorter stance phase, longer swing time, longer step length, smaller paw length, smaller intermediary toe-spread length, smaller toe-spread length, and larger foot angle right after the tenodesis procedure. After day 14, all parameters were equivalent to those of the sham-operated group. At the end of the study, there were no functional changes found in tenotomy and tenodesis groups compared with the sham-operated group and preoperative status. CONCLUSION: Transient functional alterations in temporal and spatial parameters are found after tenotomy and tenodesis in a rat model. The functional changes in the tenodesis group existed for a longer period than in tenotomy group; however, and all parameters showed no significant differences when compared with the sham group at the conclusion of the study.

Persistent trigeminal artery communicating with a fetal posterior communicating artery: A case report.

A persistent trigeminal artery (PTA) is the most common carotid-vertebrobasilar anastomosis. PTA variants terminating on cerebellar arteries instead of the basilar artery have been reported previously. We present the first case of a PTA communicating with a fetal posterior communicating artery identified on a magnetic resonance angiogram. An understanding of these anatomical variants is important to clarify pathological processes that can help guide neurosurgical and endovascular procedures.

Arthroscopic Transtendinous Biceps Tenodesis With All-Suture Anchor.

There are several methods for long head of the biceps (LHB) tenodesis, yet the optimal option is still debatable. Here we introduce a technique for arthroscopic suprapectoral biceps tenodesis with an all-suture anchor, the transtendinous biceps tenodesis technique. The LHB tenodesis is performed by using the Y-Knot anchor (1.3-mm). A standard suprapectoral approach is used for the tenodesis. A 1.3-mm drill bit is used to drill through the midportion of the biceps tendon and underlying bone to make a pilot hole. Next, the Y-Knot anchor is passed through the tendon and anchored on the underlying bone. A wrapping suture technique is then used to wrap around, tension, and secure the LHB tendon with the aid of a shuttling polydioxanone suture. The construct is fixed by tying down both suture limbs in a nonsliding fashion. This Technical Note describes an alternative method for all-arthroscopic suprapectoral biceps tenodesis using an all-suture anchor with a small diameter to minimize trauma to the tendon.

Augmentation by cerclage wire improves fixation of vertical shear femoral neck fractures-A biomechanical analysis.

BACKGROUND: Femoral neck fractures in young individuals are typically vertical shear fractures. These injuries are difficult to stabilize due to a significant varus displacement force across the hip with weight bearing. The purpose of this study was to evaluate the biomechanical stability offered by the addition of an augmented wire to conventional inverted triangle triple screw fixation for stabilizing vertical shear femoral neck fracture. METHODS: Sixteen medium 4th-generation synthetic composite femurs (Sawbones Pacific Research Laboratories, Vashon, WA) were divided into two groups. Vertical osteotomy was performed to mimic Pauwels III femoral neck fracture. Group A (n=8) was fixed with three parallel 6.5-mm cannulated screws (Stryker) with washer in inverted triangle configuration. In group B (n=8), all the screws were set using methods identical to group A, with the addition of the cerclage wire. Both groups were tested with nondestructive axial compression test at 7 and 25° of valgus stress, respectively. Then axial cyclic loading test with 1000N was applied for 1000 cycles, and interfragmentary displacement was measured with Fastrak magnetic tracking system (Polhemus, Colchester, VT, USA). Finally, destructive axial compression test was conducted at 7°of valgus stress. RESULTS: Axial stiffness showed that group B had a 66% increase (879N/mm vs. 1461N/mm, P<0.01) at 7° valgus and a 46% increase (1611N/mm vs. 2349N/mm, P<0.01) at 25° valgus in comparison with group A. Interfragmentary fracture displacement after cyclic loading was significantly less for group B compared with group A (0.34 vs 0.13mm, P=0.0016). For axial failure load, there was 42% increase in group B compared with group A (2602N/mm vs. 3686N/mm, P=0.0023). CONCLUSIONS: Our study demonstrates that the addition of a cerclage wire to inverted triangle triple screws provides substantial improvement in mechanical performance regarding fixation of vertically oriented femoral neck fractures when compared with the conventional construct. Our study provides support from a mechanical analysis perspective for the reported clinical usefulness of the cerclage wire.