Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants

Background: Growth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term. Material/methods: Infants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)−1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age. Results: In total, 49 infants (median [range] GA 25.4 [22.9–27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, β = 0.90), white matter (p = 0.007, β = 0.33), cortical gray matter (p = 0.002, β = 0.43), deep gray matter (p = 0.008, β = 0.05), and cerebellar (p = 0.006, β = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors. Conclusions: Endogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants. Impact: High serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants.IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood.Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263)

Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury.

Background: Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this post-hoc analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants. Methods: This report is an exploratory post-hoc analysis of a phase II trial in which infants <28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers. Results: The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II-III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (n = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed. Conclusion: The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start

Brain volumes and developmental outcome in childhood following fetal growth restriction leading to very preterm birth

Background: Children born very preterm (PT) after fetal growth restriction (FGR) exhibit cognitive impairment at early school age. The relationship between neurodevelopmental impairment and attained regional brain volumes is unknown. Methods: We studied 23 preterm children with FGR (PT-FGR), 24 matched preterm children AGA (PT-AGA), and 27 matched term AGA children (T-AGA) by measuring brain volumes with magnetic resonance imaging at early school age. Cognitive and motor functions were assessed by the Wechsler Intelligence Scales for Children and the ABC-Movement score. Results: The mean (SD) full-scale IQ was 80 (17) in the PT-FGR group and 103 (12) in the PT-AGA group (p < 0.001). The PT-FGR group had lower mean total, gray matter, white matter, thalamic, cerebellar white matter, and hippocampal volumes as compared to the T-AGA group (p = 0.01, 0.04, 0.003, 0.002, 0.001, and 0.009, respectively). Brain volumes did not differ significantly between the PT groups. Reduction of hippocampal volume correlated with degree of growth restriction at birth (r = 0.46, p = 0.05). Neither the full-scale IQ nor the ABC movement score <5th percentile were related to brain volumes. Conclusion: Brain volumes as determined by MRI at early school age were primarily associated with degree of prematurity at birth and less with FGR. Regional brain volumes did not discriminate cognitive and motor function beyond that predicted by gestational age at birth

Detailed anatomy at 7T

Selected high resolution axial images obtained from a 7T MRI scanner have been labeled to provide detailed information about the subtle structures found in the cerebellum and brainstem

Reconstruction of sciatic nerve after traumatic injury in humans - factors influencing outcome as related to neurobiological knowledge from animal research

Background: The aim was to evaluate what can be learned from rat models when treating patients suffering from a sciatic nerve injury.Methods: Two patients with traumatic sciatic nerve injury are presented with examination of motor and sensory function with a five-year follow-up. Reconstruction of the nerve injury was performed on the second and third day, respectively, after injury using sural nerve grafts taken from the injured leg. The patients were examined during follow-up by electromyography (EMG), MRI and functionalMRI (fMRI) to evaluate nerve reinnervation, cell death in dorsal root ganglia (DRG) and cortical activation; factors that were related to clinical history in the patients.Results: One patient regained good motor function of the lower leg and foot, confirmed by EMG showing good activation in the leg muscles and some reinnervation in the foot muscles, as well as some sensory function of the sole of the foot. The other patient regained no motor (confirmed by EMG) or sensory function in the leg or foot. Factors most influential on outcome in two cases were type of injury, nerve gap length and particularly type of reconstruction. A difference in follow-up and rehabilitation likely also influence outcome. MRI did not show any differences in DRG size of injured side compared to the uninjured side. fMRI showed normal activation in the primary somatosensory cortex as a response to cutaneous stimulation of the normal foot. However, none of the two patients showed any activation in the primary somatosensory cortex following cutaneous stimulation of the injured foot.Conclusions: In decision making of nerve repair and reconstruction data from animal experiments can be translated to clinical practice and to predict outcome in patients, although such data should be interpreted with caution and linked to clinical experience. Rat models may be useful to identify and study factors that influence outcome after peripheral nerve repair and reconstruction; procedures that should be done correctly and with a competent team. However, some factors, such as cognitive capacity and coping, known to influence outcome following nerve repair, are difficult to study in animal models. Future research has to find and develop new paths and techniques to study changes in the central nervous system after nerve injury and develop strategies to utilize brain plasticity during the rehabilitation

Health effects related to exposure of static magnetic fields and acoustic noise—comparison between MR and CT radiographers

Objectives: We explored the prevalence of health complaints subjectively associated with static magnetic field (SMF) and acoustic noise exposure among MR radiographers in Sweden, using CT radiographers as a control group. Additionally, we explored radiographers’ use of strategies to mitigate adverse health effects. Methods: A cross-sectional survey was sent to all hospitals with MR units in Sweden. MR and/or CT personnel reported prevalence and attribution of symptoms (vertigo/dizziness, nausea, metallic taste, illusion of movement, ringing sensations/tinnitus, headache, unusual drowsiness/tiredness, forgetfulness, difficulties concentrating, and difficulties sleeping) within the last year. We used logistic regression to test associations between sex, age, stress, SMF strength, working hours, and symptom prevalence. Data regarding hearing function, work-environmental noise, and strategies to mitigate adverse symptoms were also analysed. Results: In total, 529 out of 546 respondents from 86 hospitals were eligible for participation. A ≥ 20 working hours/week/modality cut-off rendered 342 participants grouped into CT (n = 75), MR (n = 121), or mixed personnel (n = 146). No significant differences in symptom prevalence were seen between groups. Working at ≥ 3T increased SMF-associated symptoms as compared with working at ≤ 1.5T (OR: 2.03, CI95: 1.05–3.93). Stress was a significant confounder. Work-related noise was rated as more troublesome by CT than MR personnel (p &lt; 0.01). MR personnel tended to use more strategies to mitigate adverse symptoms. Conclusion: No significant differences in symptom prevalence were seen between MR and CT radiographers. However, working at 3T increased the risk of SMF symptoms, and stress increased adverse health effects. Noise nuisance was considered more problematic by CT than MR personnel. Key Points: No significant differences in symptom prevalence were seen between MR and CT radiographers. Working at ≥ 3 T doubled the odds of experiencing SMF symptoms (vertigo/dizziness, nausea, metallic taste, and/or illusion of movement) as compared to working exclusively at ≤ 1.5 T. Work-related acoustic noise was less well mitigated and was rated as more troublesome by CT personnel than by MR personnel

Visualization of wrist ligaments with 3D and 2D magnetic resonance imaging at 3 Tesla

Background: Wrist ligaments are challenging to visualize using magnetic resonance imaging (MRI). Injuries involving the scapholunate ligament (SLL), the lunotriquetral ligament (LTL), and the triangular fibrocartilage complex (TFCC) are common and difficult to diagnose, often requiring diagnostic arthroscopy. Purpose: To compare the visualization of wrist ligaments on a three-dimensional (3D) sequence with two-dimensional (2D) sequences on 3-T MRI. Material and Methods: Eighteen healthy volunteers were examined with a 3D SPACE (sampling perfection with application optimized contrasts using different flip angle evolution) sequence and 2D coronal, axial, and sagittal proton density-weighted (PD) sequences. Four musculoskeletal radiologists graded the anatomical visibility of the SLL, LTL, TFCC, and the image quality, using five grades in a visual grading characteristics (VGC) evaluation. After Bonferroni correction, a P value ≤0.005 was considered statistically significant. Results: The 3D images were graded significantly better than the 2D images in the visualization of the dorsal and palmar parts of the SLL and the LTL. Regarding the TFCC, the 3D images were graded significantly better for visualization of the foveal attachment. 2D imaging was not found significantly superior to 3D imaging in any aspect. Conclusion: The 3D SPACE sequence was scored as superior to the 2D sequences at 3 T in the assessment of the SLL, the LTL, and the foveal attachment of the TFCC. Thus, 3D SPACE can replace 2D PD sequences when these ligaments need to be assessed

Improvement rates, adverse events and predictors of clinical outcome following surgery for degenerative cervical myelopathy

PURPOSE: To investigate improvement rates, adverse events and predictors of clinical outcome after laminectomy alone (LAM) or laminectomy with instrumented fusion (LAM + F) for degenerative cervical myelopathy (DCM). METHODS: This is a post hoc analysis of a previously published DCM cohort. Improvement rates for European myelopathy score (EMS) and Neck Disability Index (NDI) at 2- and 5-year follow-ups and adverse events are presented descriptively for available cases. Predictor endpoints were EMS and NDI scores at follow-ups, surgeon- and patient-reported complications, and reoperation-free interval. For predictors, univariate and multivariable models were fitted to imputed data. RESULTS: Mean age of patients (LAM n = 412; LAM + F n = 305) was 68 years, and 37.4% were women. LAM + F patients had more severe spondylolisthesis and less severe kyphosis at baseline, more surgeon-reported complications, more patient-reported complications, and more reoperations (p ≤ 0.05). After imputation, the overall EMS improvement rate was 43.8% at 2 years and 36.3% at 5 years. At follow-ups, worse EMS scores were independent predictors of worse EMS outcomes and older age and worse NDI scores were independent predictors of worse NDI outcomes. LAM + F was associated with more surgeon-reported complications (ratio 1.81; 95% CI 1.17-2.80; p = 0.008). More operated levels were associated with more patient-reported complications (ratio 1.12; 95% CI 1.02-1.22; p = 0.012) and a shorter reoperation-free interval (hazard ratio 1.30; 95% CI 1.08-1.58; p = 0.046). CONCLUSIONS: These findings suggest that surgical intervention at an earlier myelopathy stage might be beneficial and that less invasive procedures are preferable in this patient population

MRI-based measurements of spondylolisthesis and kyphosis in degenerative cervical myelopathy

Background: To provide normative data and to determine accuracy and reliability of preoperative measurements of spondylolisthesis and kyphosis on supine static magnetic resonance imaging (MRI) of patients with degenerative cervical myelopathy. Methods: T2-weighted midsagittal images of the cervical spine were in 100 cases reviewed twice by one junior observer, with an interval of 3 months, and once by a senior observer. The spondylolisthesis slip (SSlip, mm) and the modified K-line interval (mK-line INT, mm) were assessed for accuracy with the standard error of measurement (SEm) and the minimum detectable change (MDC). Intraobserver and interobserver reliability levels were determined using the intraclass correlation coefficient (ICC). Results: The SEm was 0.5 mm (95% CI 0.4-0.6) for spondylolisthesis and 0.6 mm (95% CI 0.5-0.7) for kyphosis. The MDC, i.e., the smallest difference between two examinations that can be detected with statistical certainty, was 1.5 mm (95% CI 1.2-1.8) for spondylolisthesis and 1.6 mm (95% CI 1.3-1.8) for kyphosis. The highest reliability levels were seen between the second observation of the junior examiner and the senior observer (ICC = 0.80 [95% CI 0.70-0.87] and ICC = 0.96 [95% CI 0.94-0.98] for SSlip and mK-line INT, respectively). Conclusions: This study provides normative values of alignment measurements of spondylolisthesis and kyphosis in DCM patients. It further shows the importance of taking measurement errors into account when defining cut-off values for cervical deformity parameters and their potential clinical application in surgical decision-making