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STUDY DESIGN: This is an in vitro biomechanical study. OBJECTIVE: The current investigation was performed to evaluate adjacent level kinematic change following unilateral and bilateral facet violation and laminectomy following 1-, 2-, and 3-level reconstruction. SUMMARY OF BACKGROUND DATA: The incidence of superior-segment facet violation with lumbar transpedicular fixation has been reported as high as 35%; however, its contribution to biomechanical instability at the supradjacent level is unknown. In addition, superior-segment laminectomy has been implicated as a risk factor for the development of adjacent level disease. The authors assess the acute biomechanical effects of proximal facet violation and subsequent laminectomy in an instrumented posterior fusion model in 10 cadaveric specimens. METHODS: Biomechanical testing was performed on 10 human cadaveric spines under axial rotation (AR), flexion-extension (FE), and lateral bending (LB) loading. After intact analysis, pedicle screws were inserted from L5-S1 and testing repeated with: (1) preserved L4-L5 facets, (2) unilateral facet breach, (3) bilateral breach, and (4) L5 laminectomy. Following biomechanical analysis, instrumentation was extended to L4, then L3 and biomechanical testing repeated. Full range of motion (ROM) at the proximal adjacent levels were recorded and normalized to intact (100%). RESULTS: Supradjacent level ROM was increased for all groups under all loading methods relative to intact (P < 0.05). However, AR testing revealed progressive instability at the adjacent level in groups 3 and 4, relative to group 1, following 1-, 2- and 3-level fixation (P < 0.05). During FE, supradjacent level ROM was significantly increased for group 4 specimens compared with group 1 after L5-S1 fixation (P < 0.05), and was greater than all other groups for L3-S1 constructs (P < 0.05). Interestingly, under lateral bending, facet joint destabilization did not change adjacent segment ROM. CONCLUSION: There were significant changes in proximal level ROM immediately after posterior stabilization. However, an additional increase in supradjacent segment ROM was recorded during AR after bilateral facet breach.Subsequent complete laminectomy at the uppermostfixation level further destabilized the supradjacent segment in FE and AR. Therefore, meticulous preservation of the cephalad-most segment facet joints-is paramount to ensure stability. [ABSTRACT FROM AUTHOR]

Patients with multiple sclerosis (MS) have heterogeneous clinical presentations, symptoms, and progression over time, making MS difficult to assess and comprehend in vivo. The combination of large-scale data sharing and artificial intelligence creates new opportunities for monitoring and understanding MS using MRI. First, development of validated MS-specific image analysis methods can be boosted by verified reference, test, and benchmark imaging data. Using detailed expert annotations, artificial intelligence algorithms can be trained on such MS-specific data. Second, understanding disease processes could be greatly advanced through shared data of large MS cohorts with clinical, demographic, and treatment information. Relevant patterns in such data that may be imperceptible to a human observer could be detected through artificial intelligence techniques. This applies from image analysis (lesions, atrophy, or functional network changes) to large multidomain datasets (imaging, cognition, clinical disability, genetics). After reviewing data sharing and artificial intelligence, we highlight 3 areas that offer strong opportunities for making advances in the next few years: crowdsourcing, personal data protection, and organized analysis challenges. Difficulties as well as specific recommendations to overcome them are discussed, in order to best leverage data sharing and artificial intelligence to improve image analysis, imaging, and the understanding of MS., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To examine the clinical phenotype, gray matter atrophy patterns, and small vessel disease in patients who developed prodromal or probable Alzheimer disease dementia, despite carrying the protective APOE ε2 allele., Methods: We included 36 β-amyloid-positive (by CSF or PET) APOE ε2 carriers (all ε2/ε3) with mild cognitive impairment or dementia due to Alzheimer disease who were matched for age and diagnosis (ratio 1:2) to APOE ε3 homozygotes and APOE ε4 carriers (70% ε3/ε4 and 30% ε4/ε4). We assessed neuropsychological performance across 4 cognitive domains (memory, attention, executive, and language functions), performed voxelwise and region of interest analyses of gray matter atrophy on T1-weighted MRI, used fluid-attenuated inversion recovery images to automatically quantify white matter hyperintensity volumes, and assessed T2*-weighted images to identify microbleeds. Differences in cognitive domain scores, atrophy, and white matter hyperintensities between ε2 carriers, ε3 homozygotes, and ε4 carriers were assessed using analysis of variance analyses, and Pearson χ 2 tests were used to examine differences in prevalence of microbleeds., Results: We found that ε2 carriers performed worse on nonmemory domains compared to both ε3 homozygotes and ε4 carriers but better on memory compared to ε4 carriers. Voxelwise T1-weighted MRI analyses showed asymmetric (left > right) temporoparietal-predominant atrophy with subtly less involvement of medial-temporal structures in ε2 carriers compared to ε4 carriers. Finally, ε2 carriers had larger total white matter hyperintensity volumes compared to ε4 carriers (mean 10.4 vs 7.3 mL) and a higher prevalence of microbleeds compared to ε3 homozygotes (37.5% vs 18.3%)., Conclusion: APOE ε2 carriers who develop Alzheimer disease despite carrying the protective allele display a nonamnestic clinical phenotype with more severe small vessel disease., (© 2018 American Academy of Neurology.)

Objective: To investigate serum neurofilament light chain (NfL) concentrations in frontotemporal dementia (FTD) and to see whether they are associated with the severity of disease., Methods: Serum samples were collected from 74 participants (34 with behavioral variant FTD [bvFTD], 3 with FTD and motor neuron disease and 37 with primary progressive aphasia [PPA]) and 28 healthy controls. Twenty-four of the FTD participants carried a pathogenic mutation in C9orf72 (9), microtubule-associated protein tau (MAPT; 11), or progranulin (GRN; 4). Serum NfL concentrations were determined with the NF-Light kit transferred onto the single-molecule array platform and compared between FTD and healthy controls and between the FTD clinical and genetic subtypes. We also assessed the relationship between NfL concentrations and measures of cognition and brain volume., Results: Serum NfL concentrations were higher in patients with FTD overall (mean 77.9 pg/mL [SD 51.3 pg/mL]) than controls (19.6 pg/mL [SD 8.2 pg/mL]; p < 0.001). Concentrations were also significantly higher in bvFTD (57.8 pg/mL [SD 33.1 pg/mL]) and both the semantic and nonfluent variants of PPA (95.9 and 82.5 pg/mL [SD 33.0 and 33.8 pg/mL], respectively) compared with controls and in semantic variant PPA compared with logopenic variant PPA. Concentrations were significantly higher than controls in both the C9orf72 and MAPT subgroups (79.2 and 40.5 pg/mL [SD 48.2 and 20.9 pg/mL], respectively) with a trend to a higher level in the GRN subgroup (138.5 pg/mL [SD 103.3 pg/mL). However, there was variability within all groups. Serum concentrations correlated particularly with frontal lobe atrophy rate (r = 0.53, p = 0.003)., Conclusions: Increased serum NfL concentrations are seen in FTD but show wide variability within each clinical and genetic group. Higher concentrations may reflect the intensity of the disease in FTD and are associated with more rapid atrophy of the frontal lobes., (© 2016 American Academy of Neurology.)

Study Design: Randomized, double-blinded, placebo controlled animal study., Objective: To evaluate the effect of teriparatide and calcitonin after an intertransverse process spinal fusion in a rabbit model., Summary of Background Data: It is widely recognized that some osteoporosis medications, including bisphosphonates, can interfere with bone healing. Although prescribed frequently in the treatment of osteoporosis, the effect of teriparatide and calcitonin on spinal fusion has not been fully elucidated. We hypothesized that teriparatide, being the only anabolic medication for osteoporosis treatment, would have a beneficial effect on spine fusion., Methods: Fifty-one New Zealand white rabbits underwent a posterolateral L5-L6 intertransverse process arthrodesis using autogenous iliac crest bone graft. The rabbits were randomly divided into 3 groups. All animals received daily subcutaneous injections of group I (n = 17) 1 mL of saline placebo; group II (n = 17) 10 microg/kg/day of teriparatide; group III (n = 17) 14 IU/animal of calcitonin during the 8-week postoperative period. Postmortem analyses included manual palpation, radiographic, biomechanical, and histologic assessment. Three random 10x fields were examined/graded within the cephalad, middle, and caudal regions of each section (810 fields). Fusion quality was graded using the Emery histologic scale (0-7 based on fibrous/bone content of the fusion mass)., Results: Histologic fusion rates for teriparatide averaged 86.7% and was significantly greater than the autograft control group (50%) (P = 0.033). Radiographically, there was a strong trend towards teriparatide being superior to the calcitonin group (85.7% vs. 56.3%, respectively; P = 0.07). The average Emery grading score was 5.99 +/- 1.46 SD for the autologous group and 6.26 +/- 0.93 SD for the teriparatide group (P = 0.031). Although not significant, the teriparatide group showed less motion in flexion/extension, lateral bending, and axial rotation., Conclusion: Our results suggest that teriparatide enhances spinal fusion while calcitonin has a neutral effect. The teriparatide group had the best histologic fusion rate and Emery scores, while the calcitonin group was similar to the saline controls. Although not significant, the teriparatide group had a strong trend towards superior radiographic fusion over the calcitonin group.

Study Design: In vitro cadaveric biomechanical analysis., Objective: Define the T1 and T2 anatomic lamina size and evaluate the bone-screw interface strength of various pedicle screw options and intralamina techniques., Summary of Background Data: Transpedicular instrumentation is well accepted, but salvage techniques in the proximal thoracic spine are limited. Intralamina fixation has been described at C2 with favorable biomechanical characteristics. In addition, this technique has been introduced clinically in the proximal thoracic spine. However, the biomechanical potential has not been evaluated., Methods: Fourteen fresh-frozen cervicothoracic cadaveric specimens were scanned using dual-energy radiograph absorptiometry for bone mineral density, imaged under computed tomography, and then instrumented in the following configuration: (1) Right-sided pedicle screws in a straight-forward trajectory, (2) "salvage anatomic trajectory pedicle screws, and (3) "salvage" intralamina screws into the contralateral lamina. Insertional torque (IT) was recorded with each revolution and screws were pulled out in-line (POS) with the screw axis to simulate intraoperative failure of fixation., Results: Lamina screws as a salvage technique generated statistically greater peak IT (P = 0.002) and relative POS (P < 0.05) in comparison with straight-forward transpedicular screws as the initial fixation type. Furthermore, lamina screws, when compared to the salvage anatomic trajectory pedicle screws, had a significantly greater peak IT (P = 0.011). The peak IT showed a stronger correlation with POS in lamina screws than straight-forward or anatomic pedicle screws with a similar trend noted in mean IT. Bone mineral density correlated with POS in all methods of fixation. The mean lamina width measured on computed tomography at the thinnest point was 5.9 +/- 0.7 mm (range, 4.9-7.9)., Conclusion: Our results suggest that lamina screws, used as a salvage technique in the proximal thoracic spine, provide stronger fixation than transpedicular screws when using standard 4.5-mm cervical screws. In-tralamina screws appear to be a biomechanically sound salvage technique in the region, and appear to be a safe, effective technique for instrumenting the proximal thoracic spine.

Study Design: An in vitro biomechanical cadaver study of long segment thoracic pedicle screw constructs with transverse connectors (TC)., Objective: To determine the resultant degree of motion of the instrumented thoracic spine after segmental pedicle screw instrumentation with and without TC. SUMMARY OF BACKGROUND DATA.: TC are generally not thought to be necessary with thoracic pedicle screw constructs, yet to date no study has reported the effect of TCs after all pedicle screw long thoracic fusions., Methods: Eight human cadaveric spines were potted and then instrumented from T4-T10 with bilateral 5.5 mm multiaxial titanium (Ti) pedicle screws and 5.5 mm contoured Ti rods. Specimens were tested with a six-degree-of-freedom spine stimulator in the intact condition, after instrumentation, after placement of 1 TC (3 different locations) and after placement of both TCs. Data were analyzed by loading modality (axial rotation, flexion-extension, and lateral bending) using one-way analysis of variance with an alpha of 0.05. Paired t tests were used for post hoc analysis with correction for multiple comparisons., Results: There was no difference with the addition of 1 or 2 TCs in terms of flexion-extension or lateral bending when compared to the instrumented condition (P > 0.05). Biomechanical testing of the long-segment thoracic constructs in axial rotation (torsion) loading modes generated the most significant findings of this study. After instrumentation with thoracic pedicle screws, T4-T10 full ROM was significantly reduced from the intact condition (P < 0.05). On average, TPS alone resulted in a 65% decrease in ROM. However, the addition of a transverse connector at 1 of the 3 positions tested yielded another 20% improvement in axial segmental stability as represented by further ROM reduction. These differences were significant from the TPS only group (no TCs), regardless of the TC position (P < 0.05). Furthermore, 2 TCs placed at the proximal and distal ends of the construct provided the greatest biomechanical axial stability to the instrumented specimens (P < 0.05). This was highlighted by an average of 35% ROM reduction from the stability level achieved with the TPS only constructs (P < 0.05), or an additional 15% improvement in axial stability over a single TC., Conclusion: For long thoracic pedicle screw constructs, the addition of 1 or 2 TCs significantly decreases construct axial rotation, which is the primary plane of motion for the thoracic spinal region. A single TC contributed to a significant reduction of T4-T10 ROM (an additional 20%) relative to TPS fixation alone (P < 0.05), while the location of the TC within the construct was irrelevant. A second TC had an additive effect (an additional 15% reduction) on axial stability. (P < 0.05) Flexion-extension and lateral bending are not affected. Single TC significantly improves axial rotation stability in long thoracic pedicle screw constructs. Two crosslinks, however, are better than one.