QOL-25. MICROSTRUCTURAL BRAIN CHANGES ASSOCIATED WITH NEUROCOGNITIVE AND FUNCTIONAL OUTCOMES OF INTRACRANIAL GERM CELL TUMUOR SURVIVORS – A DIFFUSIONAL KURTOSIS IMAGING STUDY

Abstract BACKGROUND Childhood intracranial germ cell tumour (iGCT) survivors are prone to radiotherapy-related neurotoxicity which can lead to neurocognitive dysfunction. Diffusion kurtosis imaging (DKI) is a MRI technique that quantifies microstructural changes in the grey and white matter of the brain. This study aims to investigate the associations between MR-DKI metrics, the cognitive and functional outcomes of childhood iGCT survivors. METHOD 20 childhood iGCT survivors who had received cranial radiotherapy were recruited. DKI parameters were determined for iGCT survivors and 18 control subjects. Neurocognitive assessment using the Hong Kong Wechsler Intelligence Scales for Children (HKWISC)/ Wechsler Adult Intelligence Scale – Revised (WAIS-R) and functional assessment using the Lansky/ Karnofsky performance scales were performed for GCT survivors. RESULTS There were significant negative correlation between the IQ scores and the mean diffusivity (MD) in multiple white matter regions of iGCT survivors including: anterior limb of internal capsule, superior fronto-occipital fasciculus, anterior corona radiata, uncinate fasciculus, cingulum and hippocampus. Mean kurtosis (MK) values of the superior fronto-occipital fasciculus were positively correlated with IQ scores. For grey matter, the MD of the olfactory, insula, caudate, heschl gyrus, parahippocampal gyrus, hippocampus, anterior cingulum, frontal inferior operculum, middle and superior temporal gyrus, middle and superior frontal orbital gyri, cuneus and precentral gyrus were negatively correlated with IQ scores. Most of the microstructural changes with associated functional impairment were white matter regions. CONCLUSION Our study identified vulnerable brain regions with significant white and grey matter microstructural changes that were associated with impaired cognitive function or deficits in physical functioning.

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Brain Microstructural Changes Associated With Neurocognitive Outcome in Intracranial Germ Cell Tumor Survivors

Frontiers in Oncology ◽

10.3389/fonc.2021.573798 ◽

2021 ◽

Vol 11 ◽

Author(s):

Winnie Wan Yee Tso ◽

Edward Sai Kam Hui ◽

Tatia Mei Chun Lee ◽

Anthony Pak Yin Liu ◽

Patrick Ip ◽

...

Keyword(s):

White Matter ◽

Germ Cell ◽

Germ Cell Tumor ◽

Grey Matter ◽

Cell Tumor ◽

Diffusion Kurtosis Imaging ◽

Functional Impairments ◽

Intracranial Germ Cell Tumor ◽

Microstructural Changes ◽

The Mean

BackgroundChildhood intracranial germ cell tumor (GCT) survivors are prone to radiotherapy-related neurotoxicity, which can lead to neurocognitive dysfunctions. Diffusion kurtosis imaging (DKI) is a diffusion MRI technique that is sensitive to brain microstructural changes. This study aimed to investigate the association between DKI metrics versus cognitive and functional outcomes of childhood intracranial GCT survivors.MethodsDKI was performed on childhood intracranial GCT survivors (n = 20) who had received cranial radiotherapy, and age and gender-matched healthy control subjects (n = 14). Neurocognitive assessment was performed using the Hong Kong Wechsler Intelligence Scales, and functional assessment was performed using the Lansky/Karnofsky performance scales (KPS). Survivors and healthy controls were compared using mixed effects model. Multiple regression analyses were performed to determine the effects of microstructural brain changes of the whole brain as well as the association between IQ and Karnofsky scores and the thereof.ResultsThe mean Intelligence Quotient (IQ) of GCT survivors was 91.7 (95% CI 84.5 – 98.8), which was below the age-specific normative expected mean IQ (P = 0.013). The mean KPS score of GCT survivors was 85.5, which was significantly lower than that of controls (P < 0.001). Cognitive impairments were significantly associated with the presence of microstructural changes in white and grey matter, whereas functional impairments were mostly associated with microstructural changes in white matter. There were significant correlations between IQ versus the mean diffusivity (MD) and mean kurtosis (MK) of specific white matter regions. The IQ scores were negatively correlated with the MD of extensive grey matter regions.ConclusionOur study identified vulnerable brain regions whose microstructural changes in white and grey matter were significantly associated with impaired cognitive and physical functioning in survivors of pediatric intracranial GCT.

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Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes

Brain ◽

10.1093/brain/awv304 ◽

2015 ◽

Vol 138 (12) ◽

pp. 3803-3815 ◽

Cited By ~ 72

Author(s):

Matthew J. Hollocks ◽

Andrew J. Lawrence ◽

Rebecca L. Brookes ◽

Thomas R. Barrick ◽

Robin G. Morris ◽

...

Keyword(s):

White Matter ◽

Functional Outcomes ◽

Microstructural Changes

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Cerebral atrophy in amyotrophic lateral sclerosis parallels the pathological distribution of TDP43

Brain Communications ◽

10.1093/braincomms/fcaa061 ◽

2020 ◽

Vol 2 (2) ◽

Cited By ~ 1

Author(s):

Mahsa Dadar ◽

Ana Laura Manera ◽

Lorne Zinman ◽

Lawrence Korngut ◽

Angela Genge ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

White Matter ◽

Motor Cortex ◽

Grey Matter ◽

Corticospinal Tract ◽

Cerebral Atrophy ◽

Precentral Gyrus ◽

Cerebral Disease ◽

Deformation Based Morphometry ◽

Lateral Sclerosis

Abstract Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by a preferential involvement of both upper and lower motor neurons. Evidence from neuroimaging and post-mortem studies confirms additional involvement of brain regions extending beyond the motor cortex. The aim of this study was to assess the extent of cerebral disease in amyotrophic lateral sclerosis cross-sectionally and longitudinally and to compare the findings with a recently proposed disease-staging model of amyotrophic lateral sclerosis pathology. Deformation-based morphometry was used to identify the patterns of brain atrophy associated with amyotrophic lateral sclerosis and to assess their relationship with clinical symptoms. Longitudinal T1-weighted MRI data and clinical measures were acquired at baseline, 4 months and 8 months, from 66 patients and 43 age-matched controls who participated in the Canadian Amyotrophic Lateral Sclerosis Neuroimaging Consortium study. Whole brain voxel-wise mixed-effects modelling analysis showed extensive atrophy patterns differentiating patients from the normal controls. Cerebral atrophy was present in the motor cortex and corticospinal tract, involving both grey matter and white matter, and to a lesser extent in non-motor regions. More specifically, the results showed significant bilateral atrophy in the motor cortex and corticospinal tract (including the internal capsule and brainstem) and ventricular enlargement, along with significant longitudinal atrophy in precentral gyrus, frontal and parietal white matter, accompanied by ventricular and sulcal enlargement. Atrophy in the precentral gyrus was significantly associated with greater disability as quantified with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (P < 0.0001). The pattern of atrophy observed using deformation-based morphometry was consistent with the Brettschneider’s four-stage pathological model of the disease. Deformation-based morphometry provides a sensitive indicator of atrophy in Amyotrophic lateral sclerosis and has potential as a biomarker of disease burden, in both grey matter and white matter.

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Supplemental Material for Wechsler Adult Intelligence Scale—Third Edition Short Form for Index and IQ Scores in a Psychiatric Population

Psychological Assessment ◽

10.1037/1040-3590.19.2.236.supp ◽

2007 ◽

Keyword(s):

Short Form ◽

Adult Intelligence Scale ◽

Intelligence Scale ◽

Wechsler Adult Intelligence Scale ◽

Adult Intelligence ◽

Iq Scores ◽

Psychiatric Population ◽

Wechsler Adult Intelligence

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A suprasellar germ cell tumour presenting with cranial diabetes insipidus

Endocrine Abstracts ◽

10.1530/endoabs.65.p321 ◽

2019 ◽

Author(s):

Suhaniya Samarasinghe ◽

Rebecca Scott ◽

Michael J Seckl ◽

Mike Gonzalez ◽

Richard Harvey ◽

...

Keyword(s):

Germ Cell ◽

Diabetes Insipidus ◽

Germ Cell Tumour ◽

Cell Tumour ◽

Cranial Diabetes Insipidus

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Cystic trophoblastic tumour: a rare presentation in the mediastinum in a post-chemotherapy patient with previous germ cell tumour in the testis

10.26226/morressier.5b4709866f4cb30010952142 ◽

2018 ◽

Author(s):

Foteini Malta

Keyword(s):

Germ Cell ◽

Germ Cell Tumour ◽

Cell Tumour ◽

Rare Presentation

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Individual differences in white and grey matter structure associated with verbal habits of thought

10.31234/osf.io/ukgyr ◽

2019 ◽

Author(s):

Justin C. Hayes ◽

Katherine L Alfred ◽

Rachel Pizzie ◽

Joshua S. Cetron ◽

David J. M. Kraemer

Keyword(s):

Individual Differences ◽

White Matter ◽

Cognitive Processing ◽

Grey Matter ◽

Structural Changes ◽

Structural Integrity ◽

Diffusion Tensor ◽

Self Report ◽

White Matter Tracts

Modality specific encoding habits account for a significant portion of individual differences reflected in functional activation during cognitive processing. Yet, little is known about how these habits of thought influence long-term structural changes in the brain. Traditionally, habits of thought have been assessed using self-report questionnaires such as the visualizer-verbalizer questionnaire. Here, rather than relying on subjective reports, we measured habits of thought using a novel behavioral task assessing attentional biases toward picture and word stimuli. Hypothesizing that verbal habits of thought are reflected in the structural integrity of white matter tracts and cortical regions of interest, we used diffusion tensor imaging and volumetric analyses to assess this prediction. Using a whole-brain approach, we show that word bias is associated with increased volume in several bilateral language regions, in both white and grey matter parcels. Additionally, connectivity within white matter tracts within an a priori speech production network increased as a function of word bias. These results demonstrate long-term structural and morphological differences associated with verbal habits of thought.

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Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-323541 ◽

2021 ◽

pp. jnnp-2020-323541

Author(s):

Jessica L Panman ◽

Vikram Venkatraghavan ◽

Emma L van der Ende ◽

Rebecca M E Steketee ◽

Lize C Jiskoot ◽

...

Keyword(s):

White Matter ◽

Frontotemporal Dementia ◽

Disease Severity ◽

Grey Matter ◽

Clinical Stage ◽

Data Driven ◽

Grey Matter Volume ◽

Matter Volume ◽

Mutation Carriers ◽

Individual Disease

ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.

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