A Longitudinal Analysis of Early Lesion Growth in Presymptomatic Patients with Cerebral Adrenoleukodystrophy.

BACKGROUND AND PURPOSE: Cerebral adrenoleukodystrophy is a devastating neurological disorder caused by mutations in the ABCD1 gene. Our aim was to model and compare the growth of early cerebral lesions from longitudinal MRIs obtained in presymptomatic patients with progressive and arrested cerebral adrenoleukodystrophy using quantitative MR imaging-based lesion volumetry. MATERIALS AND METHODS: We retrospectively quantified and modeled the longitudinal growth of early cerebral lesions from 174 MRIs obtained from 36 presymptomatic male patients with cerebral adrenoleukodystrophy. Lesions were manually segmented using subject-specific lesion-intensity thresholding. Volumes were calculated and plotted across time. Lesion velocity and acceleration were calculated between sequentially paired and triplet MRIs, respectively. Linear mixed-effects models were used to assess differences in growth parameters between progressive and arrested phenotypes. RESULTS: The median patient age was 7.4 years (range, 3.9-37.0 years). Early-stage cerebral disease progression was inversely correlated with age (ρ = -0.6631, P < .001), early lesions can grow while appearing radiographically stable, lesions undergo sustained acceleration in progressive cerebral adrenoleukodystrophy (ß = 0.10 mL/month2 [95% CI, 0.05-0.14 mL/month2], P < .001), and growth trajectories diverge between phenotypes in the presymptomatic time period. CONCLUSIONS: Measuring the volumetric changes in newly developing cerebral lesions across time can distinguish cerebral adrenoleukodystrophy phenotypes before symptom onset. When factored into the overall clinical presentation of a patient with a new brain lesion, quantitative MR imaging-based lesion volumetry may aid in the accurate prediction of patients eligible for therapy.

Sensory experiences and cues among E-cigarette users.

BACKGROUND AND AIMS: We characterized the extent and quality of respiratory sensations and sensory-related smoking cues associated with e-cigarette use among those who failed to quit combustible tobacco cigarette (CTC) use with traditional FDA approved medications but succeeded in doing so with e-cigarettes. Further, we sought to understand former smokers' perceptions about the influence of sensory experience with e-cigarette use on CTC cessation outcomes. METHODS: A nonrandom purposive sample of 156 participants recruited in the USA through the Consumer Advocates for Smoke Free Alternatives Association Facebook page completed an online cross-sectional survey to assess sensory experiences and smoking cues associated with e-cigarette use. Descriptive statistics were calculated, and the ANOVA/Kruskal-Wallis test with post hoc testing and the two-sample t test/Wilcoxon rank-sum test, as appropriate based on distribution, were used to assess the association between sample characteristics and sensory experiences and cues using investigator constructed questions, the Modified Cigarette Evaluation Questionnaire (mCEQ) and the Smoking Cue Appeal Survey (SCAS). RESULTS: With e-cigarette use, participants reported feeling the vapor in their throats, windpipes, noses, lungs, and on their tongues; reductions in nicotine craving; and enjoyment of their e-cigarette, including tasting, smelling, and seeing the vapor and touching the device. Women had greater craving reduction than men (p = 0.023). Those who began smoking at 13 years of age or younger had more satisfaction and had greater sensory enjoyment than those who began smoking at 16-17 years of age (p = 0.015 and p = 0.026, respectively), as well as greater sensory enjoyment than those who began smoking at 14-15 years of age (p = 0.047). There was a significant overall association between the number of years a respondent smoked and e-cigarette sensory enjoyment (p = 0.038). Participants 18-34 years old rated e-cigarettes as being more pleasant compared to 45 + years olds, (p = 0.012). Eighty-four percent of participants reported the sensation of the vapor as important in quitting CTCs, and 91% believed the sensations accompanying e-cigarette use contributed to their smoking cessation success. CONCLUSIONS: For those who failed to quit previously using approved cessation medications to stop smoking cigarettes, sensory experiences associated with e-cigarette use may help smokers quit smoking.

Spleen phenotype in autosomal dominant polycystic kidney disease.

AIM: To evaluate splenic phenotype in autosomal dominant polycystic kidney disease (ADPKD) including presence of cysts and splenomegaly to determine if these are ADPKD related or represent unrelated incidental findings. MATERIALS AND METHODS: The axial/coronal T2-weighted images of ADPKD patients (n=215) and age/gender-matched controls (n=215) were evaluated for the presence of T2-bright splenic lesions by three blinded observers. Spleen volume (SV) was evaluated in the context of clinical and imaging features as well as results of gene testing for PKD1 and PKD2 mutations. RESULTS: T2-bright splenic lesions were found in 16 of 215 (7%) ADPKD patients compared to 11 of 215 (5%) control patients (p=0.32) and their prevalence was similar in patients with either PKD1 or PKD2 mutations. Median SV was significantly higher in ADPKD patients than controls (236 [182; 313 ml] versus 176 [129; 264 ml], p<0.0001). In multivariable analysis, height-adjusted SV (htSV) was not associated with the presence of liver cysts, haemorrhagic cysts, or infections; however, htSV was directly associated with height-adjusted total kidney volume (htTKV), a biomarker for ADPKD disease severity. CONCLUSIONS: The prevalence of T2-bright splenic lesions is similar in ADPKD patients and non-ADPKD controls, suggesting no relation to the diagnosis of ADPKD; however, splenic enlargement in ADPKD compared to controls could not be explained by liver cystic involvement, by infection/inflammatory conditions, or by haemorrhagic renal cysts. This combined with direct correlation of htSV with htTKV, a biomarker of ADPKD severity, suggests splenomegaly may be related to the pathogenesis of ADPKD.

Quantifying Anterior Chest Wall Deformity in Adolescent Idiopathic Scoliosis: Correlation With Other Deformity Measures and Effects of Anterior Thoracoscopic Scoliosis Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study investigated how anterior chest wall deformity is affected by thoracoscopic anterior scoliosis fusion (TASF) surgery in adolescent idiopathic scoliosis patients. We aimed to determine correlations pre- and postoperatively with other clinical and radiological scoliosis measures. BACKGROUND DATA: Scoliosis surgery aims to halt progression of the deformity, and to reduce its severity. Currently, deformity correction is clinically measured in terms of Cobb angle and rib hump (RH); however, a significant cosmetic concern for patients is anterior chest wall deformity. METHODS: Pre- and postoperative CT scans of 28 female, Lenke type 1 patients with a mean preoperative Cobb angle of 50.2° ± 7.1° were retrieved from the Research Group's surgical database. Using ImageJ, 3D reconstructions of the thorax were created. Two observers measured the anterior chest wall deformity as a chest wall angle (CWA) and posterior deformity as a posterior apical deformity angle (PDA). We investigated pre- to postoperative changes in CWA, PDA, RH, and Cobb angle as well as their interrelationship. RESULTS: All deformity parameters (Cobb angle, RH, CWA, and PDA) showed statistically significant improvement post TASF. Correlation was found between RH and Cobb angle pre- and postoperatively, Cobb angle and CWA preoperatively and between postoperative change in Cobb angle and CWA. No relationship was found between CWA and RH or PDA. CONCLUSIONS: Anterior chest wall deformity is independent from the posterior chest wall measures RH and PDA, indicating that the anterior chest wall deformity is not reflected in the posterior rib cage. The correlation between Cobb angle and CWA indicates that the deformity in the spine and the deformity in the ribs are related, and shows that the anterior chest wall deformity is improved post thoracoscopic anterior scoliosis fusion surgery as the lateral deviation of the spine is corrected. LEVEL OF EVIDENCE: Level III.

The Use of Noncontrast Quantitative MRI to Detect Gadolinium-Enhancing Multiple Sclerosis Brain Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: Concerns have arisen about the long-term health effects of repeat gadolinium injections in patients with multiple sclerosis and the incomplete characterization of MS lesion pathophysiology that results from relying on enhancement characteristics alone. PURPOSE: Our aim was to perform a systematic review and meta-analysis analyzing whether noncontrast MR imaging biomarkers can distinguish enhancing and nonenhancing brain MS lesions. DATA SOURCES: Our sources were Ovid MEDLINE, Ovid Embase, and the Cochrane data base from inception to August 2016. STUDY SELECTION: We included 37 journal articles on 985 patients with MS who had MR imaging in which T1-weighted postcontrast sequences were compared with noncontrast sequences obtained during the same MR imaging examination by using ROI analysis of individual MS lesions. DATA ANALYSIS: We performed random-effects meta-analyses comparing the standard mean difference of each MR imaging metric taken from enhancing-versus-nonenhancing lesions. DATA SYNTHESIS: DTI-based fractional anisotropy values are significantly different between enhancing and nonenhancing lesions (P = .02), with enhancing lesions showing decreased fractional anisotropy compared with nonenhancing lesions. Of the other most frequently studied MR imaging biomarkers (mean diffusivity, magnetization transfer ratio, or ADC), none were significantly different (P values of 0.30, 0.47, and 0.19. respectively) between enhancing and nonenhancing lesions. Of the limited studies providing diagnostic accuracy measures, gradient-echo-based quantitative susceptibility mapping had the best performance in discriminating enhancing and nonenhancing MS lesions. LIMITATIONS: MR imaging techniques and patient characteristics were variable across studies. Most studies did not provide diagnostic accuracy measures. All imaging metrics were not studied in all 37 studies. CONCLUSIONS: Noncontrast MR imaging techniques, such as DTI-based FA, can assess MS lesion acuity without gadolinium.

Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping and R2* are sensitive to myelin and iron changes in multiple sclerosis lesions. This study was designed to characterize lesion changes on quantitative susceptibility mapping and R2* at various gadolinium-enhancement stages. MATERIALS AND METHODS: This study included 64 patients with MS with different enhancing patterns in white matter lesions: nodular, shell-like, nonenhancing < 1 year old, and nonenhancing 1-3 years old. These represent acute, late acute, early chronic, and late chronic lesions, respectively. Susceptibility values measured on quantitative susceptibility mapping and R2* values were compared among the 4 lesion types. Their differences were assessed with a generalized estimating equation, controlling for Expanded Disability Status Scale score, age, and disease duration. RESULTS: We analyzed 203 lesions: 80 were nodular-enhancing, of which 77 (96.2%) were isointense on quantitative susceptibility mapping; 33 were shell-enhancing, of which 30 (90.9%) were hyperintense on quantitative susceptibility mapping; and 49 were nonenhancing lesions < 1 year old and 41 were nonenhancing lesions 1-3 years old, all of which were hyperintense on quantitative susceptibility mapping. Their relative susceptibility/R2* values were 0.5 ± 4.4 parts per billion/-5.6 ± 2.9 Hz, 10.2 ± 5.4 parts per billion/-8.0 ± 2.6 Hz, 20.2 ± 7.8 parts per billion/-3.1 ± 2.3 Hz, and 33.2 ± 8.2 parts per billion/-2.0 ± 2.6 Hz, respectively, and were significantly different (P < .005). CONCLUSIONS: Early active MS lesions with nodular enhancement show R2* decrease but no quantitative susceptibility mapping change, reflecting myelin breakdown; late active lesions with peripheral enhancement show R2* decrease and quantitative susceptibility mapping increase in the lesion center, reflecting further degradation and removal of myelin debris; and early or late chronic nonenhancing lesions show both quantitative susceptibility mapping and R2* increase, reflecting iron accumulation.

Understanding how axial loads on the spine influence segmental biomechanics for idiopathic scoliosis patients: A magnetic resonance imaging study.

BACKGROUND: Segmental biomechanics of the scoliotic spine are important since the overall spinal deformity is comprised of the cumulative coronal and axial rotations of individual joints. This study investigates the coronal plane segmental biomechanics for adolescent idiopathic scoliosis patients in response to physiologically relevant axial compression. METHODS: Individual spinal joint compliance in the coronal plane was measured for a series of 15 idiopathic scoliosis patients using axially loaded magnetic resonance imaging. Each patient was first imaged in the supine position with no axial load, and then again following application of an axial compressive load. Coronal plane disc wedge angles in the unloaded and loaded configurations were measured. Joint moments exerted by the axial compressive load were used to derive estimates of individual joint compliance. FINDINGS: The mean standing major Cobb angle for this patient series was 46°. Mean intra-observer measurement error for endplate inclination was 1.6°. Following loading, initially highly wedged discs demonstrated a smaller change in wedge angle, than less wedged discs for certain spinal levels (+2,+1,-2 relative to the apex, (p<0.05)). Highly wedged discs were observed near the apex of the curve, which corresponded to lower joint compliance in the apical region. INTERPRETATION: While individual patients exhibit substantial variability in disc wedge angles and joint compliance, overall there is a pattern of increased disc wedging near the curve apex, and reduced joint compliance in this region. Approaches such as this can provide valuable biomechanical data on in vivo spinal biomechanics of the scoliotic spine, for analysis of deformity progression and surgical planning.

A biomechanical investigation of dual growing rods used for fusionless scoliosis correction.

BACKGROUND: The use of dual growing rods is a fusionless surgical approach to the treatment of early onset scoliosis which aims to harness potential growth and correct spinal deformity. The purpose of this study was to compare the in-vitro biomechanical response of two different dual rod designs under axial rotation loading. METHODS: Six porcine spines were dissected into seven level thoracolumbar multi-segment units. Each specimen was mounted and tested in a biaxial Instron machine, undergoing nondestructive left and right axial rotation to peak moments of 4 Nm at a constant rotation rate of 8 deg. s(-1). A motion tracking system (Optotrak) measured 3D displacements of individual vertebrae. Each spine was tested in an un-instrumented state first and then with appropriately sized semi-constrained and 'rigid' growing rods in alternating sequence. The range of motion, neutral zone size and stiffness were calculated from the moment-rotation curves and intervertebral range of motion was calculated from Optotrak data. FINDINGS: Irrespective of test sequence, rigid rods showed a significant reduction of total rotation across all instrumented levels (with increased stiffness) whilst semi-constrained rods exhibited similar rotational behavior to the un-instrumented spines (P<0.05). An 11.1% and 8.0% increase in stiffness for left and right axial rotation respectively and 14.9% reduction in total range of motion were recorded with dual rigid rods compared with semi-constrained rods. INTERPRETATION: Based on these findings, the Semi-constrained growing rods were shown to not increase axial rotation stiffness compared with un-instrumented spines. This is thought to provide a more physiological environment for the growing spine compared to dual rigid rod constructs.

Investigating the change in three dimensional deformity for idiopathic scoliosis using axially loaded MRI.

BACKGROUND: Adolescent idiopathic scoliosis is a complex three-dimensional deformity, involving a lateral deformity in the coronal plane and axial rotation of the vertebrae in the transverse plane. Gravitational loading plays an important biomechanical role in governing the coronal deformity, however, less is known about how they influence the axial deformity. This study investigates the change in three-dimensional deformity of a series of scoliosis patients due to compressive axial loading. METHODS: Magnetic resonance imaging scans were obtained and coronal deformity (measured using the coronal Cobb angle) and axial rotations measured for a group of 18 scoliosis patients (Mean major Cobb angle was 43.4°). Each patient was scanned in an unloaded and loaded condition while compressive loads equivalent to 50% body mass were applied using a custom developed compressive device. FINDINGS: The mean increase in major Cobb angle due to compressive loading was 7.4° (SD 3.5°). The most axially rotated vertebra was observed at the apex of the structural curve and the largest average intravertebral rotations were observed toward the limits of the coronal deformity. A level-wise comparison showed no significant difference between the average loaded and unloaded vertebral axial rotations (intra-observer error=2.56°) or intravertebral rotations at each spinal level. INTERPRETATION: This study suggests that the biomechanical effects of axial loading primarily influence the coronal deformity, with no significant change in vertebral axial rotation or intravertebral rotation observed between the unloaded and loaded condition. However, the magnitude of changes in vertebral rotation with compressive loading may have been too small to detect given the resolution of the current technique.

A biomechanical investigation of vertebral staples for fusionless scoliosis correction.

BACKGROUND: Fusionless scoliosis surgery is an early-stage treatment for idiopathic scoliosis which claims potential advantages over current fusion-based surgical procedures. Anterior vertebral stapling using a shape memory alloy staple is one such approach. Despite increasing interest in this technique, little is known about the effects on the spine following insertion, or the mechanism of action of the staple. The purpose of this study was to investigate the biomechanical consequences of staple insertion in the anterior thoracic spine, using in vitro experiments on an immature bovine model. METHODS: Individual calf spine thoracic motion segments were tested in flexion, extension, lateral bending and axial rotation. Changes in motion segment rotational stiffness following staple insertion were measured on a series of 14 specimens. Strain gauges were attached to three of the staples in the series to measure forces transmitted through the staple during loading. A micro-CT scan of a single specimen was performed after loading to qualitatively examine damage to the vertebral bone caused by the staple. FINDINGS: Small but statistically significant decreases in bending stiffness (P<0.05) occurred in flexion, extension, lateral bending away from the staple, and axial rotation away from the staple. Each strain-gauged staple showed a baseline compressive loading following insertion which was seen to gradually decrease during testing. Post-test micro-CT showed substantial bone and growth plate damage near the staple. INTERPRETATION: Based on our findings it is possible that growth modulation following staple insertion is due to tissue damage rather than sustained mechanical compression of the motion segment.

Spinal biomodeling.

STUDY DESIGN: A prospective trial of stereolithographic biomodeling in complex spinal surgery. OBJECTIVES: To investigate the use of stereolithographic biomodeling as an aid to complex spinal surgery. SUMMARY OF BACKGROUND DATA: Of the array of imaging methods available to assist the spinal surgeon, no single method provides a complete overview of the anatomy, although three-dimensional imaging has been shown to have advantages. METHODS: Stereolithographic biomodeling is a new technology that allows data from three-dimensional computed tomographic scans to be used to generate exact plastic replicas of anatomic structures. Five patients with complex deformities were selected: two children with congenital deformities, a patient with an osteoblastoma, a patient with basilar invagination caused by osteogenesis imperfecta, and a patient with a failed lumbar fusion. Computed tomographic scanning was performed and stereolithographic biomodels generated. The stereolithographic biomodels were used for patient education, operative planning, and surgical navigation. RESULTS: The surgeons reported that biomodeling was useful in complex spinal surgery and was an effective technology. Stereolithographic biomodels were found to be particularly useful in morphologic assessment, in the planning and rehearsal of surgery, for intraoperative navigation, and for informing patients about surgical procedures. CONCLUSIONS: Stereolithographic biomodeling allows imaging data to be displayed in a physical form. This intuitive medium may improve data display and allows surgical simulation on a proxy of the surgical site. Draw-backs of the technology were a minimum 24 hours' manufacturing time and the cost.

Pin-site complications of the halo thoracic brace with routine pin re-tightening.

STUDY DESIGN: Retrospective analysis with historic controls. OBJECTIVES: To analyze pin-site complications in a large series of halo thoracic braces in which regular re-tightening of the pins was performed. SUMMARY OF BACKGROUND DATA: Perry and Nickel first described the use of the halo thoracic brace in 1959 for cervical immobilization. Its use has been extended successfully to cervical fracture management. METHODS: A total of 266 commercially available halo thoracic braces were fitted using a standard technique. All pins were tightened routinely at 24 hours and at 1 week after application. Two data sources, prosthetic department records and patients' medical records, were analyzed. RESULTS: Six percent of patients had a pin-site infection; 3.7% had loose pins, and 1.1% reported pin-site pain. No subdural, intradural, or extradural abscess or cerebrospinal fluid leaks occurred. A total of 2.6% of halo rings slipped off, and 2.3% of patients experienced severe headaches. CONCLUSIONS: Low rates of pin-site infection, loosening, and pain were achieved through routine re-tightening of the pins. Pin re-tightening, at 24 hours and at 1 week after application, is a safe and effective method to decrease pin-site complications.

The outcome of scoliosis surgery in the severely physically handicapped child. An objective and subjective assessment.

STUDY DESIGN: A prospective, functional assessment based on physical ability and independence in daily activities was performed of patients who had severe physical handicaps and spinal deformities and were undergoing scoliosis surgery. OBJECTIVES: To determine whether improving spinal alignment and truncal balance improved the functional abilities of handicapped patients. SUMMARY OF BACKGROUND DATA: Loss of truncal stability compromises the physical independence of children who are severely handicapped. Physiologic function also may be compromised. It is not clear whether improving truncal balance actually improves their level of independence or merely halts further deterioration. METHODS: Twenty patients with significant physical handicaps resulting from neuromuscular disorders or multiple congenital anomalies and significant spinal deformity and truncal imbalance were treated surgically to realign and stabilize their spines. Their level of physical independence was evaluated before surgery, including their ability to sit, ambulate, and complete activities of daily living. Evaluation was done before surgery, 6 months after surgery, and 12 months after surgery. A subjective assessment of cosmesis also was made. RESULTS: Corrective spinal surgery resulted in a deterioration of physical ability for the first 6 months. Most patients subsequently returned to their preoperative level of function. An improvement of function exceeding their preoperative level was not seen after 12 months. The cosmetic results of surgery were excellent. CONCLUSIONS: Corrective spinal surgery in patients with severe physical handicap should be performed early to preserve function and should not be dictated solely by the severity of the curvature. Improvement in the patient's level of independence may not necessarily occur after truncal stabilization. Cosmetic results in these patients with severe disabilities were extremely gratifying to the patients and their caregivers.

Fixation of thoracolumbar fractures with the Dick fixator: the influence of transpedicular bone grafting.

Fifty patients with thoracolumbar fractures were treated by internal fixation using the Dick fixator. In the first 22 patients (group 1) this was accompanied by posterior intertransverse grafting. The technique was then modified in the following 28 patients (group 2) to include transpedicular elevation of the depressed vertebral end plate and grafting of the vertebral body, in an attempt to reduce the postoperative loss of correction of the kyphotic deformity. The clinical records and X-rays were reviewed to determine whether the change in technique had achieved this objective and whether it affected operative time, blood loss, postoperative recovery and complications. The mean operating time and blood loss in group 1 were 2 h, 38 min and 650 ml, respectively, and in group 2 2 h, 59 min and 783 ml. These differences were not statistically significant. Time from operation to mobilisation and discharge from hospital were related to neurological deficit, but there was no significant difference between group 1 and group 2 in this regard. There was no difference in the complication rate between the two groups and no complication attributable to transpedicular bone grafting. The radiological results postoperatively and at a mean follow-up period of 9 months were assessed by measurement of the kyphosis angle, anterior vertebral height, anterior displacement, scoliosis, and reduction in cross-sectional area of the spinal canal. In group 1 the mean preoperative kyphosis angle and anterior vertebral height were 8 degrees and 21 mm; postoperatively these values were -12 degrees (lordosis) and 27 mm; and at follow-up they were -4 degrees and 24 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Loss of vision in one eye following scoliosis surgery.

A 50-year-old woman developed left sided total external ophthalmoplegia and complete visual loss, with evidence of choroidal non-perfusion, immediately following scoliosis surgery. The ocular movements recovered, but the eye remained blind. It is suggested that these lesions may have resulted from pressure on the orbital contents during surgery.

Orthopaedic basis for occupationally related arm and neck pain.

A prospective clinical study of 204 individuals with occupationally related upper limb or neck pain was initiated to determine the major symptom patterns, the physical findings, and changes in laboratory tests that are exhibited by these subjects. On the basis of this information it was possible to determine the proportion that was suffering from a recognizable, pathologically discrete, musculoskeletal disorder. The study shows that in the majority (58%) of these people, a discrete musculoskeletal disorder exists. The most common diagnoses were peripheral nerve entrapments (19%) and arthropathies (16%). In 42% a discrete diagnosis was not made and the nature of the disorder, in these, is discussed.