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Background and Purpose: Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI., Materials and Methods: Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1-9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method., Results: Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) ( P < .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) ( P < .001) in the natural history cohort., Conclusions: Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease., (© 2024 by American Journal of Neuroradiology.)

Central nervous system neuroblastoma with FOXR2 activation (CNS NB FOXR2) has recently been described as a class of brain tumors sharing common genetic events and a highly similar DNA methylation profile. Most of these tumors have previously been diagnosed as primitive neuroectodermal tumor (PNET). Whereas the entity of PNET has been removed from the WHO classification of brain tumors in its current edition, CNS neuroblastoma was kept as an entity, but still lacks any molecular detail. Here, we describe 8 cases of CNS NB FOXR2 focusing on histomorphological and immunohistochemical features and include magnetic resonance imaging (MRI) for 2 of these cases. MRI revealed large supratentorial masses in superficial location with prominent cysts and necrosis, but little edema. Diffusion and enhancement characteristics were variable. Histological analyses showed that most of the cases displayed neuronal differentiation with necrosis, endothelial proliferation, and high vascularity. Immunohistochemistry revealed strong expression of synaptophysin, MAP2, and OLIG2 as well as moderate proliferation. These findings suggest that tumors with the molecular diagnosis of CNS NB FOXR2 may fit well into the WHO entity of CNS neuroblastoma. Our findings may be helpful when establishing an integrated diagnosis and may be indispensable if molecular data are unavailable., (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)

Quantitative transverse relaxation rates in normal aging brain are essential to investigate pathologies associated with iron accumulation and tissue degeneration. Since absolute values depend on imaging methods and magnetic field strengths, continuous evaluation of specific reference values remains requisite. Multi-echo turbo spin echo and multi-echo gradient recalled echo imaging sequences were applied to 66 healthy subjects (18-84years) at 3T to quantify the irreversible (R2), effective (R2*) and reversible (R2'=R2*-R2) transverse relaxation rates. Representative regions-of-interest (ROIs) were determined automatically in gray matter (GM) and white matter (WM) on T1-weighted scans. Phantom experiments of different sized iron-oxide particles were conducted to explore the correlation of R2' related to R2 for the evaluation of the size of iron deposits. R2 decreased with age for the majority of ROIs, but increased for putamen, head of caudate nucleus and nucleus accumbens. R2* and R2' increased with age in deep GM structures except for the thalamus. R2* and R2' showed a distinct dependency on fiber orientation in exemplary WM regions. R2', R2 and R2* were strongly linear proportional to age-related iron content in deep GM with slopes of 0.88, 0.18 and 1.08 in [1/s/mg Fe per 100g wet tissue] and intercepts of 1.69, 9.25 and 10.69 in [1/s], respectively. Linear and non-linear curve fitting of R2' vs. R2 in phantoms revealed increased slopes with increasing particle size. In vivo, averaged R2' vs. R2 data points of patients with Parkinson's disease and progressive supranuclear palsy were above the fitted curves of healthy subjects suggesting larger sized iron deposits in these neurodegenerative diseases. Decreased R2 with age may reflect physiological tissue degeneration, whereas increased R2* and R2' with age most likely denote physiological iron accumulation. The low intercept of R2' vs. iron content suggests a nearly sole sensitivity of R2' to iron in deep GM, potentially allowing a more specific estimation of the iron content than R2 or R2*. Since R2* and R2' depend on the fiber orientation, their feasibility to estimate iron content in WM is challenging. The analysis of R2' related to R2 may provide valuable information about the size of iron deposits., (© 2013.)

Purpose: The two most prevalent forms of neuronal ceroid lipofuscinosis (NCL) are the juvenile form (Batten disease, CLN3) and late infantile form (Jansky-Bielschowsky disease, CLN2). The aim of this study was to compare quantitative T2-values of brain tissue in CLN2 and CLN3 patients with reference values from age-matched normal subjects., Methods: Twenty-three CLN2 (n = 6) and CLN3 (n = 17) patients (m:f = 11:12) underwent MRI examination including a multiecho T2 sequence. Quantitative T2-values were measured in six defined regions of interest (ROIs) in the calculated quantitative T2 maps within the white matter (WM) and gray matter (GM). The extracted quantitative T2-values were compared with reference values from healthy children and young adults. Informed consent was obtained from the patients or their parents for all patients., Results: Statistical analysis revealed elevated quantitative T2-values in nearly all ROIs placed in the WM of the CLN2 patients. In contrast to this finding, no significant differences were found for the quantitative T2-values of the CLN3 patients compared to the age-matched healthy controls in any of the defined WM ROIs. Both groups exhibited no significant alterations of the quantitative T2-values in the GM ROIs compared to the healthy subjects., Conclusion: Alterations of quantitative T2-values in the cerebral WM may not be a reliable sign to confirm the diagnosis in CLN3 patients but could prove valuable for diagnosis confirmation, follow-up examinations, and longitudinal monitoring of the disease progression in CLN2 patients.

Distinct from signal alterations in diffusion-weighted images, T(2)-values are also dependent on tissue water content and known to increase with time from symptom onset in acute ischaemic stroke. The purpose of this study was to evaluate whether there is a detectable increase of T(2)-values in different regions in acute ischaemic stroke in the acute and subacute situation and to study the effect of recanalization on the evaluation of T(2)-values in the subacute phase. In addition, we sought to evaluate whether this increase in T(2)-values is reversible. For this purpose, 22 patients with acute ischaemic stroke in the territory of the middle cerebral artery underwent magnetic resonance imaging including diffusion-weighted imaging, perfusion-weighted imaging, fluid-attenuated inversion recovery to determine final infarct size, time-of-flight-angiography (acute and on day 1 or 2) and a triple echo-T(2)-sequence (calculation of T(2) maps) within 6 h after symptom onset. Images were co-registered and regions of diffusion restriction and prolonged time-to-peak as well as surviving tissue (surviving tissue = time-to-peak - final infarct size) and lesion growth (lesion growth = final infarct size-diffusion restriction) were defined and superimposed onto the quantitative T(2) map. In addition, patients were dichotomized according to recanalization information. Mean quantitative T(2)-values were derived for each patient within each region of interest. Mean T(2)-values for patients with recanalization (n = 15) in surviving tissue region of interest were 115.8 ± 7.2 ms (mean ± SD) and in the lesion growth region of interest 114.6 ± 7.0 ms. T(2)-values for patients without recanalization (n = 7) were 117.7 ± 11.4 ms in surviving tissue region of interest and 117.3 ± 12.1 ms in lesion growth region of interest. There was no significant difference between T(2)-values measured in lesion growth and surviving tissue region of interest for patients with or without recanalization. Even though it has been shown that T(2)-values increase with time from symptom onset within the infarct core, increased T(2)-values in areas of perfusion impairment do not identify irreversible damaged brain tissue and high T(2)-values are even found in tissue that is not part of the final infarct lesion and can therefore normalize. In conclusion, this study suggests that T(2)-values are not a valid imaging biomarker in acute stroke to predict tissue outcome.

Introduction: The aim of our work was to investigate the process of myelination in healthy patients using the diffusion parameters apparent diffusion coefficient (ADC), relative anisotropy (RA), fractional anisotropy (FA), and eigenvalues. Age-dependent changes were assessed using the slope m of the fit functions that best described the data., Materials and Methods: Seventy-two patients (3 weeks-19 years) without pathological magnetic resonance imaging findings were selected from all pediatric patients scanned with diffusion tensor imaging over a 5-year period at our institution. ADC, RA, FA, and eigenvalue maps were calculated and regions of interest were selected in anterior/posterior pons, genu/splenium of corpus callosum (CC), anterior/posterior limb of internal capsule (IC), and white matter (WM) regions (frontal, temporal, parietal, occipital WM). Statistical analysis was performed using Spearman correlation coefficient and regression analysis., Results: Mean values ranged 71.6 x 10(-5) to 90.3 x 10(-5) mm(2)/s (pons/parietal WM) for ADC, 0.32-0.94 (frontal WM/CC) for RA, and 0.36-0.81 (frontal WM/splenium) for FA. Logarithmic fit functions best described the data. Strong age influences were observed for CC, pons, and parietal/frontal WM and changes were significant for all three eigenvalues, most pronounced for perpendicular eigenvalues. Changes in RA and FA differed depending on the structure anisotropy., Conclusions: Changes observed for ADC, RA, FA, and eigenvalues with age were consistent with previous findings. Changes detected for RA and FA varied due to the different scaling of both parameters. We found that the use of the largely linear scaled RA adds more valuable information for the assessment of age-dependent structural changes as compared to FA. Additionally, we report normative values for the diffusion parameters studied.

Background: Tuberous sclerosis (TS) is characterised by benign hamartomatous lesions in many organs. Diffusion tensor imaging (DTI) can detect microstructural changes in pathological processes., Objective: To determine apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps in children with TS and to investigate the diffusion properties in cortical tubers, white-matter lesions, perilesional white matter, and contralateral normal-appearing white matter, and to compare the results with ADC and FA maps of normal age- and sex-matched volunteers., Materials and Methods: Seven children and adolescents (age range 2-20 years) suffering from TS were included. MRI was performed on a 1.5-T scanner using a transmit/receive coil with T1-W and T2-W spin-echo and FLAIR sequences. DT images were acquired by using a single-shot echo-planar pulse sequence. Diffusion gradients were applied in six different directions with a b value of 1,000 s/mm(2)., Results: ADC was higher in cortical tubers than in the corresponding cortical location of controls. ADC values were higher and FA values were lower in white-matter lesions and perilesional white matter than in both the contralateral normal-appearing white matter of patients and in controls. There were no significant differences for both ADC and FA values in the normal-appearing white matter of patients with TS compared to controls., Conclusions: DTI provides important information about cortical tubers, white-matter abnormalities, and perilesional white matter in patients with TS.

Purpose: Grey matter (GM) atrophy due to neuronal loss is a striking feature of patients with CLN3 disease. A precise and quantitative description of disease progression is needed in order to establish an evaluation tool for current and future experimental treatments. In order to develop a quantitative marker to measure brain volume outcome, we analysed the longitudinal volumetric development of GM, white matter (WM) and lateral ventricles and correlated those with the clinical course. Methods: One hundred twenty-two MRI scans of 35 patients (21 females; 14 males; age 15.3 ± 4.8 years) with genetically confirmed CLN3 disease were performed. A three-dimensional T1-weighted sequence was acquired with whole brain coverage. Volumetric segmentation of the brain was performed with the FreeSurfer image analysis suite. The clinical severity was assessed by the Hamburg jNCL score, a disease-specific scoring system. Results: The volumes of supratentorial cortical GM and supratentorial WM, cerebellar GM, basal ganglia/thalamus and hippocampus significantly (r = − 0.86 to − 0.69, p < 0.0001) decreased with age, while the lateral ventricle volume increased (r = 0.68, p < 0.0001). Supratentorial WM volume correlated poorer with age (r = − 0.56, p = 0.0001). Supratentorial cortical GM volume showed the steepest (4.6% (± 0.2%)) and most uniform decrease with strongest correlation with age (r = − 0.86, p < 0.0001). In addition, a strong correlation with disease specific clinical scoring existed for the supratentorial cortical GM volume (r = 0.85, p = < 0.0001). Conclusion: Supratentorial cortical GM volume is a sensitive parameter for assessment of disease progression even in early and late disease stages and represents a potential reliable outcome measure for evaluation of experimental therapies. [ABSTRACT FROM AUTHOR]