Amyotrophic lateral sclerosis and the frontotemporal dementias: using neuroimaging to quantitate disease progression

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1 Oxford Medicine Online You are looking at of 1902 items for: functional AND neuroimaging Can neuroimaging help distinguish bipolar depression from major depressive disorder? Matthew T. Keener and Mary L. Phillips Print Publication Year: 2009 Published Online: May 2013 ISBN: eisbn: DOI: /med/ Chapter 22 discusses the differences and similarities between depression and bipolar disorder, including how neuroimaging can help distinguish between the two. Amyotrophic lateral sclerosis and the frontotemporal dementias: using neuroimaging to quantitate disease progression S. Kalra Print Publication Year: 2012 Published Online: Nov 2012 ISBN: eisbn: DOI: /med/ After decades of clinical trials, there remains a lack of effective disease-modifying therapies for amyotrophic lateral sclerosis (ALS). In addition to the complex pathogenic mechanisms that are not fully understood, other important factors contributing to this deficiency include the lack of a sensitive and objective biomarker and the biological heterogeneity of ALS. Diagnosis is dependent on physical signs emanating from the cardinal feature of ALS: combined upper motor neurone (UMN) and lower motor neurone (LMN) degeneration. However, these signs are crude and insensitive. Additionally, UMN signs may be lacking or attenuate over time as LMN degeneration progresses. Thus, typical outcome measures in clinical trials have been composite measures of strength (e.g. manual muscle testing, maximum voluntary isometric contraction) or disability (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)), respiratory function (forced vital capacity), and survival. Drug trials based on such endpoints require hundreds of patients per study arm and are lengthy and expensive. This is a major impediment to early drug development programmes, as achieving such numbers in a timely fashion is difficult given the low prevalence of ALS. Furthermore, disability scales and survival in particular are only indirectly related to the true biological lesion (motor neurone dysfunction/death) and do not discriminate between UMN and LMN function. The heterogeneity of ALS is evident in the simple clinical observations of varied age of onset, site of symptoms onset, progression rate, and survival. This is compounded by the variable presence of frontotemporal lobar degeneration (FTLD), necessitating the Page 1 of 5

2 designation of ALS as a spectrum rather than a single disease entity. Cognitive impairment secondary to FTLD is highly prevalent and detectable by focused neuropsychometric testing in upwards of 50% of patients. Thus, variability in the clinical phenotype of ALS extends beyond that resulting from motor neurone degeneration (UMN versus LMN predominant versus mixed UMN and LMN, limb versus bulbar onset, slow versus rapid progression) to include a spectrum of cognitive and behavioural dysfunction. There have been important recent developments in elucidating the overlap of FTLD with ALS from a pathological and molecular perspective, as delineated elsewhere in this text. The clinical syndrome is better understood with consensus-based criteria now published to guide clinical evaluation. However, varying prevalence rates, conflicting reports regarding its natural history and an unclear relationship between FTLD and motor neurone degeneration make clinical measures of cognitive impairment unsuitable for monitoring disease progression. A biomarker is required to address these issues of biological and clinical heterogeneity and lack of optimal outcome measures (Table 15.1). Serum, cerebrospinal fluid, and neuroimaging biomarkers have been investigated in ALS, and are areas of intense research. Brain imaging is an obvious candidate as a biomarker of disease because: (a) it is objective; (b) it provides in vivo data; (c) it allows assessment repeatedly during the course of the disease; and (d) it allows assessment of specific regions of the brain, which is vital in understanding the impact of degeneration on behaviour. Magnetic resonance imaging techniques, in particular, are advantageous because, unlike positron emission tomography and single-photon emission tomography, they are noninvasive and do not require exposure to ionizing radiation. This chapter will review the potential role, experience, limitations, and future directions of neuroimaging in monitoring disease progression in ALS and ALS/FTLD. Discussion will be largely limited to magnetic resonance (MR) technology as longitudinal studies with other imaging modalities are scarce, most recent developments are in advanced MR methods, and MR imaging (MRI) installations are becoming ubiquitous. Principles of Psychiatry and Psychology Mary M. Machulda Print Publication Year: 2015 Published Online: Jul 2015 ISBN: eisbn: DOI: /med/ Cognition, classic psychiatric constructs, and an approach to the evaluation of cognition and psychologic disorders are discussed in this chapter. Cognitive evaluations may include simple office-based procedures, but formal neuropsychological testing and functional imaging have aided practitioners in further understanding and treating disorders as well as understanding normal function. Language Lisa Tabor Connor Print Publication Year: 2012 Published Online: Sep 2013 ISBN: eisbn: DOI: /med/ Page 2 of 5

3 This chapter discusses the neuroscience of language, including neuropsychological and lesion-symptom mapping evidence, functional neuroimaging of language and recovery, current models of language rehabilitation, treatment principles/strategies arising from neuroscience and cognitive neuroscience, and information on movement towards a neuroscientifically based model of aphasia rehabilitation. Cognitive Reserve Vanessa Raymont and Robert D Stevens Print Publication Year: 2014 Published Online: Jul 2014 ISBN: eisbn: DOI: /med/ The cognitive reserve hypothesis suggests that the structure and function of an individual s brain can modulate the clinical expression of brain damage and illness. This chapter describes passive and active models of reserve, their impact on neurological illness, and how these effects can be assessed. Passive models focus on the protective potential of anatomical features, such as brain size, neural density, and synaptic connectivity, while active models emphasize the connectivity and efficiency of neural networks and active compensation by alternative networks. It is likely that both models represent features of a common biological substrate and could help in the development of strategies to improve outcome following critical illness. Neuroimaging in the Investigation of Epilepsy Trevor T.-J. Chong and Mark Cook Print Publication Year: 2012 Published Online: Dec 2012 ISBN: eisbn: DOI: /med/ Recent advances in neuroimaging have meant that a wide variety of modalities are available to evaluate patients with epilepsy. Within this population, the key questions are whether there exists a single, resectable seizure focus and, if so, how to minimize the disruption to adjacent areas of eloquent cortex following its resection. The mainstays of structural imaging remain computerized tomography (CT) and magnetic resonance imaging (MRI), with more recently derived MR-based techniques including voxel-based morphometry (VBM), and diffusion tensor imaging (DTI) or tractography, which permit the imaging of white matter tracts. Cerebral metabolism or haemodynamics can be visualised with established techniques such as positron emission tomography (PET), single photon emission computerized tomography (SPECT), magnetic resonance spectroscopy (MRS) or functional MRI (fmri). Finally, the electrophysiological activity of the brain can be more directly imaged with magnetoencephalography (MEG) and, more recently, epileptiform discharges have also been successfully localized by performing simultaneous fmri-eeg recordings. In this chapter, we summarize the role of these modalities in managing the patient with epilepsy, and provide a synopsis of the current state of the art, including a discussion of the Page 3 of 5

4 promise and limitations of each technique. We conclude by describing the dynamic state of the neuroimaging landscape, with recent attempts at multi-modal imaging and the need for a greater evidence base to guide our choice of imaging modalities in individual patients. Neurobiology of Early-onset Mood Disorders Frank P. MacMaster, David R. Rosenberg, and Joan Kaufman Print Publication Year: 2010 Published Online: Jun 2013 ISBN: eisbn: DOI: /med/ Chapter 9 summarizes the extant data concerning the neurobiology of early-onset mood disorders and discusses the treatment implications of the emerging findings. Integration and ConsolidationA Neurophysiological Model of Bipolar Disorder Stephen M. Strakowski Print Publication Year: 2012 Published Online: Jun 2013 ISBN: eisbn: DOI: /med/ Bipolar disorder is one of the most common and disabling conditions affecting humankind. Although defined by the occurrence of mania, it is characterized by a dynamic course of illness in which affective, cognitive and neurovegetative symptoms wax and wane. The illness typically starts in adolescence and progresses during its early years from rare to increasingly common affective episodes. Bipolar disorder is strongly familial, suggesting that it originates from specific genetic risk factors, although these have not yet been well defined. Together, these characteristics suggest that bipolar disorder involves dysfunction within ventral prefrontal networks that modulate limbic brain structures. Moreover, this dysfunction appears to arise during critical developmental stages in brain development, likely reflecting the impact of specific genes that underlie brain growth and development, monamine control, circadian rhythm regulation or related functions. In this chapter, then, we converge evidence from neuroimaging and genetic studies to develop a specific neurophysiological model of bipolar disorder to guide future investigations. Amyotrophic lateral sclerosis Martin R. Turner Print Publication Year: 2015 Published Online: Apr 2015 ISBN: eisbn: DOI: /med/ Since the cerebellum modulates several functions from motor control to cognition, its degeneration has devastating effects. Neuroimaging has helped to characterize the anatomical pathology of different types of degenerative ataxias. In hereditary ataxias, the value of imaging data lies in its contribution to our understanding of the disease process by objectively monitoring the progression of neurodegeneration and providing surrogate Page 4 of 5

5 markers to monitor therapeutic efficacy. Neuroimaging helps with differential diagnosis in sporadic ataxias and in those patients with hereditary ataxias where a family history is not available. In this chapter we review the MRI methods most frequently used to study degenerative ataxias and we also discuss future trends of analysis highlighting its potential utility with selected examples from the literature. Neuroimaging of Autism Spectrum Disorder Nicole R. Zürcher and Jacob M. Hooker Print Publication Year: 2016 Published Online: Feb 2016 ISBN: eisbn: DOI: /med/ Neuroimaging studies have reported atypicalities in neurotransmitter systems, brain anatomy, and brain function in individuals with autism spectrum disorder (ASD) across all ages, but a biomarker has yet to be discovered. Discovery of a biomarker, a pathophysiological mechanism common to individuals with ASD or a subgroup of individuals with ASD, could potentially help in early diagnosis and the development of more targeted pharmacological or behavioral interventions. This chapter examines the types of information that can be obtained using the following neuroimaging techniques: magnetic resonance imaging, electroencephalography, and positron emission tomography/ single-photon emission computed tomography. After an introduction to the techniques, a discussion of the advantages of each technique and an overview of key findings in ASD research are provided. Page 5 of 5

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