External Capsule Research Articles

PATTERNS OF INfiLTRATION AND RELAPSE OF GLIOBLASTOMA INVOLVING THE ANTERIOR TEMPORAL LOBE: IMPLICATIONS FOR RADIATION THERAPY TARGET VOLUME DELINEATION

Abstract AIMS To characterise specific patterns of infiltration and recurrence for IDH-wildtype Glioblastoma (GBMwt) involving the anterior temporal lobe (ATL) METHOD Patients managed for GBMwt involving ATL between 1/2008-12/2020 were identified. Tumour was segmentated on T1-gadolinium-enhanced(T1gd) and T2-weighted(T2) sequences at baseline and initial relapse. Involvement of adjacent normal structures was assessed: superior temporal gyrus (STG), middle temporal gyrus (MTG), medial occipito-temporal gyrus (MOTG), amygdala, and uncus. Abnormalities in para- hippocampal region (PHG) and sub-insular regions were recorded; as well as distant sites of insular cortex, extreme/external/internal capsule, and frontal lobe. Two major neural pathways were also assessed: the uncinate fasciculus-inferior fronto-occipital fasciculus (UF- IFOF) and hippocampal formation (HP-PHG). RESULTS Of 562 patients 53 involved ATL with 47 included for analysis. Median volume at diagnosis on T1gd and T2 was 36cm3(IQR 12-54) and 51cm3(IQR 23-73) respectively. Adjacent sites involved on T1gd were STG/MTG (87%), amygdala (45%), uncus (8%), MOTG (4%). T2 abnormality extended into insular region in 91%, and hippocampal region in 17% patients. The temporal horn was involved in 21% and compressed/displaced in 63% of patients. Forty patients relapsed with relapse-free survival of 11.4 months. Thirty-five (87%) had T1gd relapse involving a neural pathway: UF-IFOF (74%), HP-PHG (14%), combined (9%), optic tract (3%). Twenty relapses (50%) involved distant sites in external capsule or frontal lobe. Although adjacent to ATL, no relapse occurred posterior to temporal horn or along HP-PHG unless evidence of T2 abnormality was present at diagnosis. All 8 relapses involving the HP-PHG, and none of 26 relapses involving UF-IFOF alone, had T2 involvement of HP-PHG at diagnosis. CONCLUSIONS Infiltration and relapse of GBMwt involving ATL correlates with distinct neural pathways.

Quantification of myelination in children with attention-deficit/hyperactivity disorder: a comparative assessment with synthetic MRI and DTI.

Evaluation of myelin content is crucial for attention-deficit/hyperactivity disorder (ADHD). To estimate myelin content in ADHD based on synthetic MRI-based method and compare it with established diffusion tensor imaging (DTI) method. Fifth-nine ADHD and fifty typically developing (TD) children were recruited. Global and regional myelin content (myelin volume fraction [MVF] and myelin volume [MYV]) were assessed using SyMRI and compared with DTI metrics (fractional anisotropy and mean/radial/axial diffusivity). The relationship between significant MRI parameters and clinical variables were assessed in ADHD. No between-group differences of whole-brain myelin content were found. Compared to TDs, ADHD showed higher mean MVF in bilateral internal capsule, external capsule, corona radiata, and corpus callosum, as well as in left tapetum, left superior fronto-occipital fascicular, and right cingulum (all PFDR-corrected < 0.05). Increased MYV were found in similar regions. Abnormalities of DTI metrics were mainly in bilateral corticospinal tract. Besides, MVF in right retro lenticular part of internal capsule was negatively correlated with cancellation test scores (r = -0.41, P = 0.002), and MYV in right posterior limb of internal capsule (r = 0.377, P = 0.040) and left superior corona radiata (r = 0.375, P = 0.041) were positively correlated with cancellation test scores in ADHD. Increased myelin content underscored the important pathway of frontostriatal tract, posterior thalamic radiation, and corpus callosum underlying ADHD, which reinforced the insights into myelin quantification and its potential role in pathophysiological mechanism and disease diagnosis. Prospectively registered trials number: ChiCTR2100048109; date: 2021-07.

White matter microstructural alterations in patients with neuropathic pain after spinal cord injury: a diffusion tensor imaging study.

Through contrastive analysis, we aimed to identify the white matter brain regions that show microstructural changes in patients with neuropathic pain (NP) after spinal cord injury (SCI). We categorized patients with SCI into NP (n = 30) and non-NP (n = 15) groups. We extracted diffusion tensor maps of fractional anisotropy (FA) and mean (MD), axial (AD), and radial (RD) diffusivity. A randomization-based method in tract-based spatial statistics was used to perform voxel-wise group comparisons among the FA, MD, AD, and RD for nonparametric permutation tests. Atlas-based analysis located significantly different regions (p < 0.05) in the appointed brain atlas. Compared to the non-NP group, the NP group showed higher FA in the posterior body and splenium of the corpus callosum and higher AD in the corpus callosum, internal capsule, corona radiata, posterior thalamic radiation, sagittal stratum, external capsule, cingulum, fornix/stria terminalis, superior longitudinal fasciculus, and uncinate fasciculus. The results demonstrated that compared with the non-NP group, NP pathogenesis after SCI was potentially related to higher values in FA that are associated with microstructural changes in the posterior body and splenium of the corpus callosum, which could be regarded as central sensitization or network hyperexcitability.

Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes.

Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI. T2-weighted imaging, diffusion tensor imaging (DTI), and perfusion weighted imaging (PWI) were performed. Adult Sprague-Dawley rats were imaged sequentially on days 3, 14, and 1, 4, 6, 8, and 12 months following surgery. TBI caused dynamic white and gray matter alterations with significant differences in DTI values and injury-induced alterations in cerebral blood flow (CBF) as measured by PWI. Regional abnormalities after TBI were observed in T2-weighted images that showed hyperintense cortical lesions and significant cerebral atrophy in these hyperintense areas 1 year after TBI. Temporal DTI values indicated significant injury-induced changes in anisotropy in major white matter tracts, the corpus callosum and external capsule, and in gray matter, the hippocampus and cortex, at both early and chronic time points. These alterations were primarily injury-severity dependent with severe TBI exhibiting a greater degree of change relative to uninjured controls. PWI evaluating CBF revealed sustained global reductions in the cortex and in the hippocampus at most time points in an injury-independent manner. We next sought to investigate prognostic correlations across MRI metrics, timepoints, and cerebral pathology, and found that diffusion abnormalities and reductions in CBF significantly correlated with specific vulnerable structures at multiple time points, as well as with the degree of cerebral atrophy observed 1 year after TBI. This study further supports using DTI and PWI as a means of prognostic imaging for progressive structural changes after TBI and emphasizes the progressive nature of TBI damage.

Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study

BackgroundStroke is a major cause of mortality and long-term disability worldwide. Whether the associations between brain imaging-derived phenotypes (IDPs) and stroke are causal is uncertain.MethodsWe performed two-sample bidirectional Mendelian randomization (MR) analyses to explore the causal associations between IDPs and stroke. Summary data of 587 brain IDPs (up to 33,224 individuals) from the UK Biobank and five stroke types (sample size range from 301,663 to 446,696, case number range from 5,386 to 40,585) from the MEGASTROKE consortium were used.ResultsForward MR indicated 14 IDPs belong to projection fibers or association fibers were associated with stroke. For example, higher genetically determined mean diffusivity (MD) in the right external capsule was causally associated with an increased risk of small vessel stroke (IVW OR = 2.76, 95% CI 2.07 to 3.68, P = 5.87 × 10−12). Reverse MR indicated that genetically determined higher risk of any ischemic stroke was associated with increased isotropic or free water volume fraction (ISOVF) in body of corpus callosum (IVW β = 0.23, 95% CI 0.14 to 0.33, P = 3.22 × 10−7). This IDP is a commissural fiber and it is not included in the IDPs identified by forward MR.ConclusionsWe identified 14 IDPs with statistically significant evidence of causal effects on stroke or stroke subtypes. We also identified potential causal effects of stroke on one IDP of commissural fiber. These findings might guide further work toward identifying preventative strategies at the brain imaging levels.

Indoleamine 2,3-Dioxygenase Deletion to Modulate Kynurenine Pathway and to Prevent Brain Injury after Cardiac Arrest in Mice.

The catabolism of the essential amino acid tryptophan to kynurenine is emerging as a potential key pathway involved in post-cardiac arrest brain injury. The aim of this study was to evaluate the effects of the modulation of kynurenine pathway on cardiac arrest outcome through genetic deletion of the rate-limiting enzyme of the pathway, indoleamine 2,3-dioxygenase. Wild-type and indoleamine 2,3-dioxygenase-deleted (IDO-/-) mice were subjected to 8-min cardiac arrest. Survival, neurologic outcome, and locomotor activity were evaluated after resuscitation. Brain magnetic resonance imaging with diffusion tensor and diffusion-weighted imaging sequences was performed, together with microglia and macrophage activation and neurofilament light chain measurements. IDO-/- mice showed higher survival compared to wild-type mice (IDO-/- 11 of 16, wild-type 6 of 16, log-rank P = 0.036). Neurologic function was higher in IDO-/- mice than in wild-type mice after cardiac arrest (IDO-/- 9 ± 1, wild-type 7 ± 1, P = 0.012, n = 16). Indoleamine 2,3-dioxygenase deletion preserved locomotor function while maintaining physiologic circadian rhythm after cardiac arrest. Brain magnetic resonance imaging with diffusion tensor imaging showed an increase in mean fractional anisotropy in the corpus callosum (IDO-/- 0.68 ± 0.01, wild-type 0.65 ± 0.01, P = 0.010, n = 4 to 5) and in the external capsule (IDO-/- 0.47 ± 0.01, wild-type 0.45 ± 0.01, P = 0.006, n = 4 to 5) in IDO-/- mice compared with wild-type ones. Increased release of neurofilament light chain was observed in wild-type mice compared to IDO-/- (median concentrations [interquartile range], pg/mL: wild-type 1,138 [678 to 1,384]; IDO-/- 267 [157 to 550]; P < 0.001, n = 3 to 4). Brain magnetic resonance imaging with diffusion-weighted imaging revealed restriction of water diffusivity 24 h after cardiac arrest in wild-type mice; indoleamine 2,3-dioxygenase deletion prevented water diffusion abnormalities, which was reverted in IDO-/- mice receiving l-kynurenine (apparent diffusion coefficient, μm2/ms: wild-type, 0.48 ± 0.07; IDO-/-, 0.59 ± 0.02; IDO-/- and l-kynurenine, 0.47 ± 0.08; P = 0.007, n = 6). The kynurenine pathway represents a novel target to prevent post-cardiac arrest brain injury. The neuroprotective effects of indoleamine 2,3-dioxygenase deletion were associated with preservation of brain white matter microintegrity and with reduction of cerebral cytotoxic edema.

White matter microstructural disruption in minimal hepatic encephalopathy: a neurite orientation dispersion and density imaging (NODDI) study.

To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI.

3.0 T prostate MRI: Visual assessment of 2D and 3D T2-weighted imaging sequences using PI-QUAL score

PurposeComparing 2D and 3D T2 weighted sequences in terms of image quality in 3.0 T MRI with readers of varied experiences, using PI-QUAL inspired criteria. Methods91 male patients with suspected prostate cancer (PCa) underwent diagnostic prostate MRI on a 3.0 T MR system using a 32-channel phased-array torso coil before prostate biopsy. MRI protocol included 3D T2w images, axial 2D T2w images, axial diffusion-weighted images (DWI) with the corresponding ADC apparent diffusion coefficient maps, and axial dynamic contrast enhanced images. 3D T2w and 2D T2w imaging were compared by 4 radiologists using a Likert scale for image quality (overall anatomy, delineation of capsule, seminal vesicles, ejaculatory ducts, sphincter muscle, artifacts), tumor delimitation and conspicuity. ResultsNo significant differences in terms of overall quality between 3D and 2D T2w images were found. However 2D T2w demonstrated higher rating than 3D T2w images as for the image quality of the external capsule, sphincter muscle and ejaculatory ducts delineation (p < 0.05). Conclusion3D T2w sequence can’t replace 2D T2w sequence, despite good quality images but it remains more prone to artifacts. Quality of 2D T2w sequences was substantially superior to 3D sequences for delineation of key structures as external capsule, sphincter muscle. The use of PI-QUAL criteria allows reproducible analysis of the quality of T2 weighted images.

A Twin Study of Altered White Matter Heritability in Youth With Autism Spectrum Disorder

White matter alterations are frequently reported in autism spectrum disorder (ASD), yet the etiology is currently unknown. The objective of this investigation was to examine, for the first time, the impact of genetic and environmental factors on white matter microstructure in twins with ASD compared to control twins without ASD. Diffusion-weighted MRIs were obtained from same-sex twin pairs (6-15 years of age) in which at least 1 twin was diagnosed with ASD or neither twin exhibited a history of neurological or psychiatric disorders. Fractional anisotropy (FA) and mean diffusivity (MD) were examined across different white matter tracts in the brain, and statistical and twin modeling were completed to assess the proportion of variation associated with additive genetic (A) and common/shared (C) or unique (E) environmental factors. We also developed a novel Twin-Pair Difference Score analysis method that produces quantitative estimates of the genetic and environmental contributions to shared covariance between different brain and behavioral traits. Good-quality data were available from 84 twin pairs, 50 ASD pairs (32 concordant for ASD [16 monozygotic; 16 dizygotic], 16 discordant for ASD [3 monozygotic; 13 dizygotic], and 2 pairs in which 1 twin had ASD and the other exhibited some subthreshold symptoms [1 monozygotic; 1 dizygotic]) and 34 control pairs (20 monozygotic; 14 dizygotic). Average FA and MD across the brain, respectively, were primarily genetically mediated in both control twins (A= 0.80, 95% CI [0.57, 1.02]; A= 0.80 [0.55, 1.04]) and twins concordant for having ASD (A= 0.71 [0.33, 1.09]; A= 0.84 [0.32,1.36]). However, there were also significant tract-specific differences between groups. For instance, genetic effects on commissural fibers were primarily associated with differences in general cognitive abilities and perhaps some diagnostic differences for ASD because Twin-Pair Difference-Score analysis indicated that genetic factors may have contributed to ∼40% to 50% of the covariation between IQ scores and FA of the corpus callosum. Conversely, the increased impact of environmental factors on some projection and association fibers were primarily associated with differences in symptom severity in twins with ASD; for example, our analyses suggested that unique environmental factors may have contributed to ∼10% to 20% of the covariation between autism-related symptom severity and FA of the cerebellar peduncles and external capsule. White matter alterations in youth with ASD are associated with both genetic contributions and potentially increased vulnerability or responsivity to environmental influences. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. The author list of this paper includes contributors from the location and/or community where the research was conducted and they participated in the data collection, design, analysis, and/or interpretation of the work.

Study of the relationship between onset lateralization and hemispheric white matter asymmetry in Parkinson's disease.

Parkinson's disease (PD) is characterized by a lateralized onset, but its cause and mechanism are still unclear. Obtaining diffusion tensor imaging (DTI) data from the Parkinson's Progression Markers Initiative (PPMI). Tract-based spatial statistics analysis and region-of-interest-based analysis were performed to evaluate the white matter (WM) asymmetry using original DTI parameters, Z Score normalized parameters, or the asymmetry index (AI). Hierarchical cluster analysis and least absolute shrinkage and selection operator regression were performed to construct predictive models for predicting the PD onset side. DTI data from The Second Affiliated Hospital of Chongqing Medical University were obtained for external validation of the prediction model. 118 PD patients and 69 healthy controls (HC) from PPMI were included. Right-onset PD patients presented more asymmetric areas than left-onset PD patients. The inferior cerebellar peduncle (ICP), superior cerebellar peduncle (SCP), external capsule (EC), cingulate gyrus (CG), superior fronto-occipital fasciculus (SFO), uncinate fasciculus (UNC), and tapetum (TAP) showed significant asymmetry inleft-onset and right-onset PD patients. An onset-side-specific pattern of WM alterations exists in PD patients, and a prediction model was constructed. The predicting models based on AI and ΔZ Score presented favorable efficacy in predicting PD onset side by external validation in 26 PD patients and 16 HCs from our hospital. Right-onset PD patients may have more severe WM damage than left-onset PD patients. WM asymmetry in ICP, SCP, EC, CG, SFO, UNC, and TAP may predict PD onset side. Imbalances in the WM network may underlie the mechanism of lateralized onset in PD.

Resistance Training Maintains White Matter and Physical Function in Older Women with Cerebral Small Vessel Disease: An Exploratory Analysis of a Randomized Controlled Trial.

As the aging population grows, there is an increasing need to develop accessible interventions against risk factors for cognitive impairment and dementia, such as cerebral small vessel disease (CSVD). The progression of white matter hyperintensities (WMHs), a key hallmark of CSVD, can be slowed by resistance training (RT). We hypothesize RT preserves white matter integrity and that this preservation is associated with improved cognitive and physical function. To determine if RT preserves regional white matter integrity and if any changes are associated with cognitive and physical outcomes. Using magnetic resonance imaging data from a 12-month randomized controlled trial, we compared the effects of a twice-weekly 60-minute RT intervention versus active control on T1-weighted over T2-weighted ratio (T1w/T2w; a non-invasive proxy measure of white matter integrity) in a subset of study participants (N = 21 females, mean age = 69.7 years). We also examined the association between changes in T1w/T2w with two key outcomes of the parent study: (1) selective attention and conflict resolution, and (2) peak muscle power. Compared with an active control group, RT increased T1w/T2w in the external capsule (p = 0.024) and posterior thalamic radiations (p = 0.013) to a greater degree. Increased T1w/T2w in the external capsule was associated with an increase in peak muscle power (p = 0.043) in the RT group. By maintaining white matter integrity, RT may be a promising intervention to counteract the pathological changes that accompany CSVD, while improving functional outcomes such as muscle power.

Higher Dose Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation Increases Feeding Volumes and White Matter Microstructural Complexity in Open-Label Study of Infants Slated for Gastrostomy Tube

To determine whether transcutaneous auricular vagus nerve stimulation (taVNS) paired with twice daily bottle feeding increases the volume of oral feeds and white matter neuroplasticity in term-age-equivalent infants failing oral feeds and determined to need a gastrostomy tube. In this prospective, open-label study, 21 infants received taVNS paired with 2 bottle feeds for 2 - 3weeks (2x). We compared 1) increase oral feeding volumes with 2x taVNS and previously reported once daily taVNS (1x) to determine a dose response, 2) number of infants who attained full oral feeding volumes, and 3) diffusional kurtosis imaging and magnetic resonance spectroscopy before and after treatment by paired t tests. All 2x taVNS treated infants significantly increased their feeding volumes compared with 10days before treatment. Over 50% of 2x taVNS infants achieved full oral feeds but in a shorter time than 1x cohort (median 7 days [2x], 12.5days [1x], P<.05). Infants attaining full oral feeds showed greater increase in radial kurtosis in the right corticospinal tract at the cerebellar peduncle and external capsule. Notably, 75% of infants of diabetic mothers failed full oral feeds, and their glutathione concentrations in the basal ganglia, a measure of central nervous system oxidative stress, were significantly associated with feeding outcome. In infants with feeding difficulty, increasing the number of daily taVNS-paired feeding sessions to twice-daily significantly accelerates response time but not the overall response rate of treatment. taVNS was associated with white matter motor tract plasticity in infants able to attain full oral feeds. Clinicaltrials.gov (NCT04643808).

Neuroimaging of complications arising after CD19 chimeric antigen receptor T-cell therapy: A review.

Chimeric antigen receptor (CAR) T cells targeting the CD19 (cluster of differentiation 19) cell surface glycoprotein have emerged as a highly effective immunologic therapy in patients with relapsed or refractory B-cell malignancies. The engagement of CAR T cells with CD19 on the surface of neoplastic B cells causes a systemic cytokine release, which can compromise the blood-brain barrier and cause an immune effector cell-associated neurotoxicity syndrome (ICANS). In a small proportion of ICANS patients who demonstrate neuroimaging abnormalities, certain distinct patterns have been recognized, including signal changes in the thalami, external capsule, and brainstem, the subcortical and/or periventricular white matter, the splenium of the corpus callosum, and the cerebellum. On careful review of the underlying pathophysiology of ICANS, we noticed that these changes closely mirror the underlying blood-brain barrier disruption and neuroinflammatory and excitotoxic effects of the offending cytokines released during ICANS. Furthermore, other uncommon complications of CD19 CAR T-cell therapy such as posterior reversible encephalopathy syndrome, ocular complications, and opportunistic fungal infections can be catastrophic if not diagnosed in a timely manner, with neuroimaging playing a significant role in management. In this narrative review, we will summarize the current literature on the spectrum of neuroimaging findings in ICANS, list appropriate differential diagnoses, and explore the imaging features of other uncommon central nervous system complications of CD19 CAR T-cell therapy using illustrative cases from two tertiary care institutions.

The neurodegeneration of the cholinergic pathways in subtypes of subjective cognitive decline

AbstractBackgroundNeurodegeneration of cholinergic pathways may be present in individuals with subjective cognitive decline (SCD). However, variability between SCD individuals in the integrity of cholinergic pathways needs to be elucidated. Our objective was to determine characteristics of neurodegeneration of cholinergic pathways in different SCD subtypes (i.e. amnestic vs. non‐amnestic).MethodIndividuals with amnestic SCD (n = 47), non‐amnestic SCD (n = 38), and healthy controls without cognitive complaints (HC; n = 20) from the GENIC database were included (all: &gt;60 years old; 58% females). White matter integrity was estimated by mean diffusivity (MD) on diffusion tensor imaging (DTI) for cingulum and external cholinergic pathways. Both pathways were previously modelled using tractography on DTI. Memory performance was measured based on Visual reproduction WMS‐III and TAVEC (the Spanish version of the California Verbal Learning Test, CVLT). ANOVA and bivariate Pearson correlation were used for the statistical analysis.ResultAmnestic and non‐amnestic SCD groups were comparable to HC in the integrity of cholinergic WM pathways. Bivariate Pearson correlation analyses showed different patterns of association between the cholinergic pathways and cognition within each group. In amnestic‐SCD, worse WM integrity in both cholinergic pathways was associated with poorer immediate recall of visual information (external capsule: rxy = ‐0.42; p&lt;0.05; cingulum: rxy = ‐0.34; p&lt;0.05). In non‐amnestic‐SCD, worse WM integrity in both cholinergic pathways was associated with poorer delayed recall of verbal information (external capsule: rxy = ‐0.54; p&lt;0.05; cingulum: rxy = ‐0.42; p&lt;0.05); and worse WM integrity in the external capsule pathway was associated with poorer performance in immediate and delayed recall of visual information (rxy = ‐0.37; p&lt;0.05 and rxy = ‐0.46; p&lt;0.05). In HC, none of the cognitive outcomes was associated with the integrity of the cholinergic pathways.ConclusionThe cholinergic pathways were mainly associated with immediate recall in the amnestic SCD (i.e. acquisition of new information); whereas in non‐amnestic SCD the integrity of cholinergic pathways was associated with several subcomponents of memory performance (i.e. acquisition and recall of new information). Thus, SCD subtypes show unique patterns of associations between poorer integrity of the cholinergic system and memory performance.

Improved Myelination following Camp Leg Power, a Selective Motor Control Intervention for Children with Spastic Bilateral Cerebral Palsy: A Diffusion Tensor MRI Study.

Children with spastic cerebral palsy have motor deficits associated with periventricular leukomalacia indicating WM damage to the corticospinal tracts. We investigated whether practice of skilled lower extremity selective motor control movements would elicit neuroplasticity. Twelve children with spastic bilateral cerebral palsy and periventricular leukomalacia born preterm (mean age, 11.5 years; age range, 7.3-16.6 years) participated in a lower extremity selective motor control intervention, Camp Leg Power. Activities promoted isolated joint movement including isokinetic knee exercises, ankle-controlled gaming, gait training, and sensorimotor activities (3 hours/day, 15 sessions, 1 month). DWI scans were collected pre- and postintervention. Tract-Based Spatial Statistics was used to analyze changes in fractional anisotropy, radial diffusivity, axial diffusivity, and mean diffusivity. Significantly reduced radial diffusivity (P < . 05) was found within corticospinal tract ROIs, including 28.4% of the left and 3.6% of the right posterior limb of the internal capsule and 14.1% of the left superior corona radiata. Reduced mean diffusivity was found within the same ROIs (13.3%, 11.6%, and 6.6%, respectively). Additionally, decreased radial diffusivity was observed in the left primary motor cortex. Additional WM tracts had decreased radial diffusivity and mean diffusivity, including the anterior limb of the internal capsule, external capsule, anterior corona radiata, and corpus callosum body and genu. Myelination of the corticospinal tracts improved following Camp Leg Power. Neighboring WM changes suggest recruitment of additional tracts involved in regulating neuroplasticity of the motor regions. Intensive practice of skilled lower extremity selective motor control movements promotes neuroplasticity in children with spastic bilateral cerebral palsy.

Compromised white matter is related to lower cognitive performance in adults with phenylketonuria.

Despite increasing knowledge about the effects of phenylketonuria on brain structure and function, it is uncertain whether white matter microstructure is affected and if it is linked to patients' metabolic control or cognitive performance. Thus, we quantitatively assessed white matter characteristics in adults with phenylketonuria and assessed their relationship to concurrent brain and blood phenylalanine levels, historical metabolic control and cognitive performance. Diffusion tensor imaging and 1H spectroscopy were performed in 30 adults with early-treated classical phenylketonuria (median age 35.5 years) and 54 healthy controls (median age 29.3 years). Fractional anisotropy and mean, axial and radial diffusivity were investigated using tract-based spatial statistics, and white matter lesion load was evaluated. Brain phenylalanine levels were measured with 1H spectroscopy whereas concurrent plasma phenylalanine levels were assessed after an overnight fast. Retrospective phenylalanine levels were collected to estimate historical metabolic control, and a neuropsychological evaluation assessed the performance in executive functions, attention and processing speed. Widespread reductions in mean diffusivity, axial diffusivity and fractional anisotropy occurred in patients compared to controls. Mean diffusivity and axial diffusivity were decreased in several white matter tracts and were most restricted in the optic radiation (effect size rrb = 0.66 to 0.78, P < 0.001) and posterior corona radiata (rrb = 0.83 to 0.90, P < 0.001). Lower fractional anisotropy was found in the optic radiation and posterior corona radiata (rrb = 0.43 to 0.49, P < 0.001). White matter microstructure in patients was significantly associated with cognition. Specifically, inhibition was related to axial diffusivity in the external capsule (rs = -0.69, P < 0.001) and the superior (rs = -0.58, P < 0.001) and inferior longitudinal fasciculi (rs = -0.60, P < 0.001). Cognitive flexibility was associated with mean diffusivity of the posterior limb of the internal capsule (rs = -0.62, P < 0.001), and divided attention correlated with fractional anisotropy of the external capsule (rs = -0.61, P < 0.001). Neither concurrent nor historical metabolic control was significantly associated with white matter microstructure. White matter lesions were present in 29 out of 30 patients (96.7%), most often in the parietal and occipital lobes. However, total white matter lesion load scores were unrelated to patients' cognitive performance and metabolic control. In conclusion, our findings demonstrate that white matter alterations in early-treated phenylketonuria persist into adulthood, are most prominent in the posterior white matter and are likely to be driven by axonal damage. Furthermore, diffusion tensor imaging metrics in adults with phenylketonuria were related to performance in attention and executive functions.

Painful Hemidystonia - A Rare Presentation of Uremic Encephalopathy (P5-9.011)

<h3>Objective:</h3> We describe a patient who presented with right painful hemidystonia secondary to uremic encephalopathy. We describe their presentation, clinical course and management with accompanying video. <h3>Background:</h3> Uremic encephalopathy has been associated with basal ganglia abnormalities that cause movement disorders to include chorea, tremor, and asterixis. To date, hemidystonia secondary to uremic encephalopathy, particularly in the pediatric population, has not been described. <h3>Design/Methods:</h3> A ten-year-old girl with Goldenhar syndrome (oculo-auriculo-vertebral syndrome) was admitted with acute respiratory failure which progressed to cardiac arrest leading to multiorgan failure including end stage renal disease requiring continuous renal replacement therapy (CRRT). After a brief period of recovery following extubation, she developed action tremor of the hands followed by painful right hemidystonia. Imaging following the onset of symptoms revealed new parenchymal signal abnormalities with increased T2 hyperintensities affecting the bilateral (left greater than right) caudate nuclei, globus pallidus, putamen, and left external capsule. Review of lab results revealed a correlation between the development of symptoms and a significant increase in urea and creatinine levels from baseline. She was treated with oral clonazepam and targeted botulinum neurotoxin injections with clinically meaningful benefit and closer regulation of electrolytes. Over the coming weeks, her cardiac function and renal function continued to decline, and care was redirected. <h3>Results:</h3> Painful hemidystonia, although rare, can be a presentation of uremic encephalopathy due to basal ganglia involvement. This patient showed symptomatic improvement with oral benzodiazepines and botulinum neurotoxin injections. <h3>Conclusions:</h3> Uremic encephalopathy can present with various movement disorders including chorea, tremor, asterixis and painful hemidystonia with basal ganglia involvement and should be considered in patients with worsening renal function. <b>Disclosure:</b> Dr. Sudheendra has nothing to disclose. Dr. Hull has received publishing royalties from a publication relating to health care.

P031 Montelukast antagonising underlying systemic illness

Abstract Background/Aims Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, multisystemic, autoimmune vasculitis involving small to medium-sized blood vessels. It has a well-established affiliation with atopic syndromes, typically adult-onset asthma and sinusitis. More rare associations are linked with drug side effects such as Montelukast. According to the ‘American College of Rheumatology 1990’, the following criteria yield a sensitivity of 84% in identifying a patient with EGPA. The criteria include: asthma, eosinophilia &amp;gt;10% on differential white cell count, mononeuropathy or polyneuropathy, transient pulmonary infiltrates on chest radiography, paranasal sinus abnormality, and blood vessel biopsy demonstrating extravascular eosinophilia, in a patient with symptoms of systemic vasculitis. The multisystemic involvement of EGPA makes both diagnosis and management difficult as presentations can vary. Methods We report the complex case of a 61 year-old gentleman diagnosed with EGPA. His relevant past medical history includes a diagnosis of Asthma in 2002 (managed with inhaled bronchodilators, corticosteroids, and montelukast), recurrent sinusitis, and lower respiratory tract infections. The patient presented with a one month history of abdominal cramping and bloating. This was associated with nausea, constipation, anorexia, and a week of ‘drenching’ night sweats. His full physical examination during this time was unremarkable. Results He had a normal CT Abdomen Pelvis and colonoscopy. His admission chest radiograph demonstrated bilateral parenchymal lung changes. This was followed by a CT Thorax showing bilateral upper and lower lobe bronchiectasis. Mediastinal and hilar adenopathy consistent with a diagnosis of allergic bronchopulmonary aspergillosis with associated reactive adenopathy. His laboratory investigations showed eosinophilia (21.68) and leucocytosis (32.7). In view of these results, an autoantibody screen was sent showing positive ANCA and positive anti-Myeloperoxidase antibodies(MPO titre 55). Two days into his admission he developed pain and paralysis of his right upper limb. He reported marked fatigue followed by a petechial, non-blanching, vasculitic rash on both ankles. Neurological examination reflected a subacute symmetrical sensory and motor polyneuropathy predominantly involving the right side with bilateral foot drop. MRI Brain demonstrated an established infarct in the left external capsule. He was commenced on high dose aspirin. Due to high suspicion for EGPA, methylprednisolone was commenced for 5 days, followed by tapering oral corticosteroid therapy and Rituximab therapy. A skin punch biopsy showed ‘ a vasculopathic type reaction with small vessel vasculitis, associated mixed inflammatory infiltrate which includes some eosinophils’ confirmed his diagnosis. Conclusion A topic of particular relevance to this case is the association between EGPA and montelukast. It has been hypothesised that there may be a relationship between Leukotriene Receptor Antagonist Therapy, specifically Montelukast, with the pathogenesis of EGPA. Some research suggests that treatment with Montelukast permits the decreased need for oral corticosteroids for asthma control. Therefore, suggesting that EGPA could have been masked by corticosteroid therapy. Disclosure Á. Connerton: None.

Magnetic-resonance imaging semiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in subjects from Russian Federation

Introduction. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is common variant of small vessel disease. Determination of neuroimaging markers have already contributed at an early stage to the more timely diagnosis of the CADASIL.Objective. The aim of the study was to determine probable CADASIL magnetic resonance imaging (MRI) biomarkers for patients from the Russian population.Material and methods. The study included 16 patients. Diagnosis of CADASIL was suspected based on clinical data and an MRI and confi rmed by a molecular genetic study of the NOTCH3 gene. Brain MRI data from 16 patients and spinal cord MRI data from 5 patients were collected and analyzed. Cerebrospinal fl uid (CSF) analysis was performed for diff erential diagnosis in 2 subjects.Results. White matter hyperintensity was observed in 100% of cases. The involvement of the anterior temporal lobes and external capsules was revealed in 62 and 68% of subjects respectively. Multiple lacunar infarcts are characteristic for CADASIL. Microbleeds were detected in 27% of patients. Brain atrophy was observed in 56% of cases. Lesions in corpus callosum and cervical spinal cord were found in 2 patients.Conclusion. Detection of white matters hyperintensities in frontal and parietal lobes, multiple lacunar infarcts with suspected CADASIL makes it possible to select the group of patients for further molecular genetic testing in order to detect mutations in NOTCH3 gene.

Early recovery of cognition and brain plasticity after surgery in children with low-grade frontal lobe tumors.

Low-grade frontal lobe tumors (LGFLT) can be cured through total resection, but surgical trauma could impair higher-order cognitive function. We aim to characterize the short-term natural cognitive recovery and brain plasticity in surgically-treated pediatric patients with LGFLT. Ten pediatric patients with LGFLT were enrolled. Their cognitive function was assessed before the surgery (S0), in the first month post-surgery (S1), and 3-6 months post-surgery (S2), using the CNS Vital Signs battery. DTI and rs-fMRI were performed during the same time periods. Changes of cognition and image metrics between S1>S0 and S2>S1 were analyzed. The Motor Speed (MotSp) and Reaction Time (RT) scores significantly decreased in S1 and recovered in S2. Rs-fMRI showed decreased functional connectivity (FC) between the bilateral frontal lobes and bilateral caudates, putamina, and pallidi in S1>S0 (voxel threshold , cluster threshold ). In S2>S1, FC recovery was observed in the neighboring frontal cortex areas ( , ). Among them, the FC in the caudates-right inferior frontal gyri was positively correlated to the RT ( ). A DTI Tract-based spatial statistics (TBSS) analysis showed decreased fractional anisotropy and axial diffusivity mainly in the corticospinal tracts, cingulum, internal capsule, and external capsule at 0-6 months post-surgery (TFCE- ). The DTI metrics were not associated with the cognitive data. Processing speed impairment after an LGFLT resection can recover naturally within 3-6 months in school-age children. Rs-fMRI is more sensitive to short-term brain plasticity than DTI TBSS analysis. "Map expansion" plasticity in the frontal-basal ganglia circuit may contribute to the recovery.