Posterior Fossa Horns in Hurler Syndrome: Prevalence and Regression.

Posterior fossa "horns" caused by internal hypertrophy of the occipitomastoid sutures are one of the more recently defined cranial abnormalities described in mucopolysaccharidoses, especially in Hurler Syndrome. However, details of this finding, including the development and natural history, are not well-understood. Two hundred eighty-six brain MR imaging studies of 61 patients with mucopolysaccharidosis I-Hurler syndrome treated at single institution between 1996 and 2015 were studied. Posterior fossa horn height was measured as the perpendicular distance from the tip of the horn to the expected curvature of the occipital inner table. Fifty-seven of the 61 patients (93.4%) had evidence of posterior fossa horns on at least one occasion. The initial average height of the right horn was 4.5 mm, and the left horn, 4.7 mm. Most of the posterior horns regressed before transplantation in our cohort, though the exact age was variable among the patients. Nearly all patients in our cohort had posterior fossa horns, and these horns regressed with age. The regression of the horns frequently started before transplantation. This trend has not been previously described, and it may suggest unknown effects of mucopolysaccharidosis on skull development.

Dilated Optic Nerve Sheath in Mucopolysaccharidosis I: Common and Not Necessarily High Intracranial Pressure.

Hydrocephalus is one of the earliest manifestations of mucopolysaccharidosis I-Hurler syndrome, and delayed treatment of hydrocephalus can lead to neurocognitive delay or even death. Optic nerve sheath diameter has been established as a noninvasive measurement to detect elevated intracranial pressure. This study aimed to establish correlations between optic nerve sheath diameter and opening pressure. Forty-nine MR images and opening pressures in patients with mucopolysaccharidosis I-Hurler syndrome were retrospectively reviewed from 2008 to 2020. The optic nerve sheath diameter was measured 3 mm posterior to the posterior margin of the globe (retrobulbar) and 10 mm anterior to the optic foramen (midpoint segment), and the average was taken between the 2 eyes. Opening pressure was measured with the patient in the lateral decubitus position with controlled end-tidal CO2 on the same day as the MR imaging. The average retrobulbar optic nerve sheath diameter was 5.33 mm, higher than the previously reported measurement in healthy controls, in patients with idiopathic intracranial hypertension, and there was a positive correlation between age and the optic nerve sheath diameter measured at the retrobulbar or midpoint segment (retrobulbar segment, R 2 = 0.27, P < .01; midpoint segment, R 2 = 0.20, P < .01). However, there was no correlation between retrobulbar or midpoint segment optic nerve sheath diameter and opening pressure (retrobulbar segment, R 2 = 0.02, P = .17; midpoint segment, R 2 = 0.03, P < .12). This study shows a higher average optic nerve sheath diameter in patients with mucopolysaccharidosis I-Hurler syndrome than in healthy controls regardless of the location of the measurement. However, the degree of optic nerve sheath dilation does not correlate with opening pressure, suggesting that increased optic nerve sheath diameter is an ocular manifestation of mucopolysaccharidosis I-Hurler syndrome itself rather than a marker of elevated intracranial pressure.

Susceptibility-Weighted Imaging of the Pediatric Brain after Repeat Doses of Gadolinium-Based Contrast Agent.

BACKGROUND AND PURPOSE: Gadolinium complexes have paramagnetic properties; thus, we aimed to determine the susceptibility changes in the globus pallidus and dentate nucleus following administration of linear or macrocyclic gadolinium-based contrast agents in children. MATERIALS AND METHODS: Thirty-three patients with linear gadolinium-based contrast agent gadopentetate dimeglumine administration, 33 age- and sex-matched patients with macrocyclic gadolinium-based contrast agent gadobutrol administration, and 33 age- and sex-matched control subjects without gadolinium exposure were enrolled in this retrospective study. The signal intensity on SWI and T1WI was determined in the dentate nucleus, middle cerebellar peduncle, globus pallidus, and pulvinar of the thalamus in an ROI-based analysis to calculate dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios. A repeated measures ANOVA was performed to compare SWIminimum, SWImean, and T1WI signal intensity ratios between gadolinium-based contrast agent groups and control subjects. Pearson correlation analysis was performed to determine any correlation between signal intensity ratios and variables. RESULTS: Dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios for both SWImean and SWIminimum were lower for the linear gadolinium-based contrast agent group compared with macrocyclic gadolinium-based contrast agent and control groups (P < .05). No significant difference of the SWImean and SWIminimum ratios were noted between the macrocyclic gadolinium-based contrast agent group and the control group (P > .05). Both dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios on T1WI in the linear gadolinium-based contrast agent group were higher than in the control group and the macrocyclic gadolinium-based contrast agent group (P < .05). A negative correlation was identified between SWImean and SWIminimum ratios and the number of linear gadolinium-based contrast agent administrations (dentate nucleus-to-middle cerebellar peduncle ratio: SWImean, r = -0.43, P = .005; SWIminimum, r = -0.38, P = .011; globus pallidus-to-thalamus ratio: SWImean, r = -0.39, P = .009; SWIminimum, r = -0.33, P = .017). CONCLUSIONS: SWI analysis of the pediatric brain demonstrated a statistically significant decrease in SWIminimum and SWImean values for the dentate nucleus and globus pallidus after administration of linear gadolinium-based contrast agents but not macrocyclic gadolinium-based contrast agents.

Evaluation of anatomical landmark position differences for head computed tomography: A reliability study among technologists.

INTRODUCTION: In computed tomography (CT) imaging protocols, lack of practice standards and variability in head positioning may all yield substantial inter-study image variance in the clinical setting which may limit the diagnostic and comparative value of subsequent scans. We aimed to evaluate repeatability of multiplanar reformatting of head CT based on the tuberculum sella (TS) to internal occipital protuberance (IOP) reference line and reduce variance. METHODS: Reference lines that correspond to the TS-IOP plane on high-resolution CT scans were reviewed by technologists manually to calculate Yaw (z-rotation, rotation along the superoinferior direction), Pitch (x-rotation, rotation along the left-right direction), and Roll (y-rotation, rotation along the anteroposterior direction) angles in this pre-post design intervention study. The Yaw, Pitch, and Roll angles deviating from the reference TS-IOP in the head CT images before and after technologist training were measured with the technologists' actual graphical prescriptions, and their differences were calculated with t-tests. The intra-rater agreement was calculated using the intraclass correlation coefficient (ICC). RESULTS: Mean pitch, yaw, and roll before technologist training was 6.7° ± 5.4°, 0.9° ± 1.5°, and 1.1° ± 1.2° and after training were 3.2° ± 2.6°, 0.6° ± 1.1°, and 0.6° ± 1.1°, respectively. Technologist training resulted in a significant decrease in pitch (p < 0.001) and roll (p = 0.001) inter-subject variability with respect to the TS-IOP line, however no significant difference for the yaw correction (p = 0.065) was noted. Intra-rater agreement regarding the reproducibility of TS-IOP reformation was excellent (ICC>0.950). CONCLUSION: TS-IOP reference line corrected for direct roll, yaw, and pitch can be readily achieved by trained technologists. IMPLICATIONS FOR PRACTICE: Adoption of the TS-IOP reference line should facilitate intra- and intermodality comparisons, leading to more reproducible and readily interpretable CT images.

Pseudo-Leptomeningeal Contrast Enhancement at 3T in Pediatric Patients Sedated by Propofol.

BACKGROUND AND PURPOSE: Propofol is a cerebral vasoconstrictor that modulates cerebral perfusion by decreasing the metabolic rate of oxygen. Because younger children often undergo intravenous sedation for MR imaging, this study set out to evaluate the degree of leptomeningeal contrast enhancement on 3T postcontrast brain MR imaging and to determine whether this phenomenon relates to sequence, sedation dosage, or patient age or weight. MATERIALS AND METHODS: During a 2-year period, of 152 children 1-5 years of age who underwent MR imaging, 43 were included for MRI review. Of these, 37 underwent postcontrast imaging with either solely gradient-echo T1WI (n = 20) or spin-echo T1WI (n = 17); notably, 6 patients underwent both sequences. Three neuroradiologists separately graded the degree of leptomeningeal contrast enhancement (grades 0-3) that was correlated with various factors and calculated the interobserver reliability. RESULTS: For the 43 patients, the mean patient age was 3.1 ± 1.4 years. The leptomeningeal contrast-enhancement grade was significantly greater (P < .0001) on spin-echo T1WI (1.9-2.1) versus gradient-echo TIWI (1.2-1.4). Patient weight (r = -0.366 to -.418, P = .003-.01) and age (r = -0.315 to -0.418, P = .004-.032) moderately and inversely correlated with the leptomeningeal contrast-enhancement grade, while the propofol dosage, sedation duration, and time to T1WI post-contrast administration did not (each, P > .05). The interobserver κ was strong regarding the leptomeningeal contrast-enhancement grade on both spin-echo T1WI (κ = 0.609-0.693, P < .0001) and gradient-echo TIWI (κ = 0.567-0.698, P < .0001). CONCLUSIONS: Leptomeningeal contrast enhancement (or "pseudo"-leptomeningeal contrast enhancement) occurs with a greater frequency and degree on 3T postcontrast spin-echo T1WI relative to gradient-echo TIWI in younger children sedated with propofol and should not be mistaken for disease. This phenomenon may be more prominent with lower age or size and may arise from propofol-induced vascular smooth-muscle dilation.

Transforaminal Lumbar Puncture: An Alternative Technique in Patients with Challenging Access.

Interlaminar lumbar puncture and cervical puncture may not be ideal in all circumstances. Recently, we have used a transforaminal approach in selected situations. Between May 2016 and December 2017, twenty-six transforaminal lumbar punctures were performed in 9 patients (25 CT-guided, 1 fluoroscopy-guided). Seven had spinal muscular atrophy and were referred for intrathecal nusinersen administration. In 2, CT myelography was performed via transforaminal lumbar puncture. The lumbar posterior elements were completely fused in 8, and there was an overlying abscess in 1. The L1-2 level was used in 2; the L2-3 level, in 10; the L3-4 level, in 12; and the L4-5 level, in 2 procedures. Post-lumbar puncture headache was observed on 4 occasions, which resolved without blood patching. One patient felt heat and pain at the injection site that resolved spontaneously within hours. One patient had radicular pain that resolved with conservative treatment. Transforaminal lumbar puncture may become an effective alternative to classic interlaminar lumbar puncture or cervical puncture.

Childhood Cerebral Adrenoleukodystrophy: MR Perfusion Measurements and Their Use in Predicting Clinical Outcome after Hematopoietic Stem Cell Transplantation.

BACKGROUND AND PURPOSE: MR perfusion has shown abnormalities of affected WM in cerebral X-linked adrenoleukodystrophy, but serial data is needed to explore the import of such findings after hematopoietic stem cell transplantation. Our aim was to prospectively measure MR perfusion parameters in patients with cerebral adrenoleukodystrophy pre- and post-hematopoietic stem cell transplantation, and to correlate those measurements with clinical outcome. MATERIALS AND METHODS: Ten patients with cerebral adrenoleukodystrophy prospectively underwent DSC-MR perfusion imaging at <45 days pre- (baseline), 30-60 days post-, and 1 year post-hematopoietic stem cell transplantation. MR perfusion measurements in the 10 patients and 8 controls were obtained from the parieto-occipital WM, splenium of the corpus callosum, leading enhancing edge, and normal-appearing frontal white matter. MR imaging severity scores and clinical neurologic function and neurocognitive scores were also obtained. MR perfusion values were analyzed in the patients with cerebral adrenoleukodystrophy at each time point and compared with those in controls. Correlations were calculated between the pre-hematopoietic stem cell transplantation MR perfusion values and 1-year clinical scores, with P value adjustment for multiple comparisons. RESULTS: At baseline in patients with cerebral adrenoleukodystrophy, both relative CBV and relative CBF within the splenium of the corpus callosum and parieto-occipital WM significantly differed from those in controls (P = .005-.031) and remained so 1 year post-hematopoietic stem cell transplantation (P = .003-.005). Meanwhile, no MR perfusion parameter within the leading enhancing edge differed significantly from that in controls at baseline or at 1 year (P = .074-.999) or significantly changed by 1 year post-hematopoietic stem cell transplantation (P = .142-.887). Baseline Loes scores correlated with 1-year clinical neurologic function (r = 0.813, P < .0001), while splenium of the corpus callosum relative CBV also significantly correlated with 1-year neurologic function scale and the neurocognitive full-scale intelligence quotient and performance intelligence quotient scores (r = -0.730-0.815, P = .007-.038). CONCLUSIONS: Leading enhancing edge measurements likely remain normal post-hematopoietic stem cell transplantation in cerebral adrenoleukodystrophy, suggesting local disease stabilization. Meanwhile, parieto-occipital WM and splenium of the corpus callosum relative CBV and relative CBF values worsened; this change signified irreversible injury. Baseline splenium of the corpus callosum relative CBV may predict clinical outcomes following hematopoietic stem cell transplantation.

Intensity of MRI Gadolinium Enhancement in Cerebral Adrenoleukodystrophy: A Biomarker for Inflammation and Predictor of Outcome following Transplantation in Higher Risk Patients.

BACKGROUND AND PURPOSE: Outcomes following hematopoietic stem cell transplantation for higher risk childhood-onset cerebral adrenoleukodystrophy are variable. We explored whether a brain MR imaging gadolinium intensity scoring system improves prediction of neurologic outcome. MATERIALS AND METHODS: We developed a 4-point scale of gadolinium intensity relative to the choroid plexus: 0 = no enhancement; 1 = hypointense; 2 = isointense; 3 = hyperintense. The interobserver concordance of the scale was assessed on 30 randomly chosen studies. Scores were generated for 64 evaluable patients and compared with CSF chitotriosidase levels, a known inflammatory marker correlating with outcomes following transplantation. For 25 evaluable higher risk patients (Loes ≥10), the gadolinium intensity score was compared with longer term posttransplantation clinical change. RESULTS: The gadolinium intensity scoring system showed good interobserver reproducibility (κ = 0.72). Of 64 evaluable boys, the score positively correlated with average concomitant CSF chitotriosidase activity in nanograms/milliliter/hour: 0: 2717, n = 5; 1: 3218, n = 13; 2: 6497, n = 23; and 3: 12,030, n = 23 (P < .01). For 25 evaluable higher risk patients, more intense pretransplantation brain MR imaging gadolinium enhancement predicted greater average loss on the adrenoleukodystrophy neurologic function scale following transplantation: 0/1: adrenoleukodystrophy neurologic function scale score difference = 4.3, n = 7; 2/3: adrenoleukodystrophy neurologic function scale score difference = 10.4, n = 18 (P = .05). CONCLUSIONS: Gadolinium enhancement intensity on brain MR imaging can be scored simply and reproducibly for cerebral adrenoleukodystrophy. The enhancement score significantly correlates with chitotriosidase. In boys with higher risk cerebral disease (Loes ≥10), the enhancement score itself predicts neurologic outcome following treatment. Such data may help guide treatment decisions for clinicians and families.

Childhood cerebral X-linked adrenoleukodystrophy: diffusion tensor imaging measurements for prediction of clinical outcome after hematopoietic stem cell transplantation.

BACKGROUND AND PURPOSE: DTI in cerebral X-linked adrenoleukodystrophy may demonstrate abnormalities in both affected and nonaffected WM; these values have not been studied serially after hematopoietic stem cell transplantation. The purpose of this study was to study pretransplant and posttransplant DTI parameters serially and ultimately to determine the ability of pretransplant DTI parameters to predict clinical outcome after HSCT in children with ALD. MATERIALS AND METHODS: Eight patients with posterior-pattern cerebral ALD underwent DTI at 3T before HSCT (T0), at 30-60 days (T1), 90-120 days (T2), 180 days (T3), and 1 year (T4) after HSCT. FA and MD were serially measured in 19 regions, and these measurements were compared with those in control patients. MR imaging severity (Loes) scores were recorded. Correlations were performed between DTI parameters and Loes scores, neurologic function scores, and several neuropsychologic scores. RESULTS: Both FA and MD in subjects differed significantly from that in controls at nearly every time point within cerebellar WM, callosal splenium, and parieto-occipital WM; FA alone was significantly different at each time point within the optic radiations, lateral geniculate, and the Meyer loop (P < .05). Loes scores at T0 correlated strongly with each clinical score at T4 (r = 0.771-0.986, P < .05). The only significant DTI correlation at T0 with a clinical score at T4 was callosal body FA with adaptive function (r = 0.976, P < .001). Correlating the change in DTI values with change in NFS (change between T0 and T4) showed that only ΔMD within the optic radiations correlated strongly with ΔNFS (r = 0.903, P < .05). CONCLUSIONS: DTI values at T0 were generally poor predictors of outcome at 1 year, whereas Loes scores were generally good predictors. ΔMD within the optic radiations strongly correlates with ΔNFS over that year. In addition, certain normal-appearing regions, such as cerebellar WM, may have DTI abnormalities before HSCT that persist after HSCT.

MR imaging findings in the reticular formation in siblings with MPV17-related mitochondrial depletion syndrome.

Hepatocerebral MPV17-MDS is quite rare (<30 confirmed cases), with limited findings described on MR imaging. We report 2 siblings having abnormalities within the reticular formation of the lower brain stem and within the reticulospinal tracts at the cervicocranial junction on T2WI. The presence of these MR imaging findings (relative to previous reports) raises the possibility that they represent subtle but characteristic findings corresponding to clinically observed abnormalities of tone encountered with this recently described disorder.