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Evaluation of Upper Motor Neuron Pathology in Amyotrophic Lateral Sclerosis by MRI: Towards Identifying Noninvasive Biomarkers of the Disease

Rajagopalan, Venkateswaran
http://rave.ohiolink.edu/etdc/view?acc_num=csu1288020485

Abstract Details

2010, Doctor of Engineering, Cleveland State University, Fenn College of Engineering.
Amyotrophic lateral sclerosis (ALS) is the commonest adult motor neuron disease (MND) which causes progressive muscle paralysis and death usually within 5 years of symptom onset. As a result, only ~30,000 individuals in the United States are afflicted at any one time even though 5,000 or more individuals are diagnosed yearly. The diagnosis of ALS requires evidence of degeneration in upper motor neurons (UMNs) in the brain and in lower motor neurons (LMNs) that exit the brainstem and spinal cord to innervate skeletal muscles. Diagnosis can be incorrect or delayed when disease is early or atypical because non-invasive objective tests of UMN involvement do not exist, unlike electromyography to assess the LMN. Although magnetic resonance imaging (MRI) of brain and spinal cord is used primarily to identify conditions which mimic ALS, novel MRI sequences and post-processing techniques can identify macroscopic and even sub-macroscopic changes in ALS brain related to neuronoaxonal degeneration (e.g., in corticospinal motor tracts). MRI-based techniques like diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H-MRS), as well as nuclear medicine modalities like positron emission tomography (PET) and single photon emission tomography (SPECT) are being used to study brains of patients with ALS. Many previous MRI studies of ALS brain are limited either in methodology or information obtained being primarily qualitative, i.e. changes visible to the naked eye (macroscopic). This study employed both routine and novel MRI sequences to objectively assess gray and white matter pathology of the brain in ALS patients, including T2 relaxometry, DTI, and voxel based morphometry (VBM) of 3D high resolution T1-weighted images. DTI metrics showed significant (p<0.05) changes in rostral extent of corticospinal tract (CST) in ALS patients with predominantly UMN symptoms and signs, and the ALS-dementia patients, whereas more caudal involvement was observed in ALS patients with classic findings of UMN and LMN dysfunction. Significant (p<0.05) grey matter volume and cortical thickness reductions were observed only in the ALS dementia group when compared to controls, which suggests that neurodegeneration might begin as a neuronopathy in these patients. Preserved grey matter volume and cortical thickness in other ALS patients suggests a dying back axonopathy and warrants further study. To our knowledge this is the first study in a large number of ALS patients categorized into different subgroups based on their clinical presentation. Future comparisons of brain MRI and post-mortem histopathology in the same patient will allow radiopathologic correlation of tissue pathology underlying the radiographic changes, including CST hyperintensity. These may reveal differences in pathogenic mechanisms causing ALS which could respond differently to novel pharmacotherapies.
Guang Yue, PhD (Committee Chair)
Erik Pioro, MD PhD (Advisor)
George Chatzimavroudis, PhD (Committee Member)
Randolph Setser, D.Sc (Committee Member)
Andrew Slifkin (Committee Member)
145 p.
Biomedical Research
MRI; UMN; LMN; DTI; CST

Recommended Citations

Citations

  • Rajagopalan, V. (2010). Evaluation of Upper Motor Neuron Pathology in Amyotrophic Lateral Sclerosis by MRI: Towards Identifying Noninvasive Biomarkers of the Disease [Doctoral dissertation, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1288020485

    APA Style (7th edition)

  • Rajagopalan, Venkateswaran. Evaluation of Upper Motor Neuron Pathology in Amyotrophic Lateral Sclerosis by MRI: Towards Identifying Noninvasive Biomarkers of the Disease. 2010. Cleveland State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1288020485.

    MLA Style (8th edition)

  • Rajagopalan, Venkateswaran. "Evaluation of Upper Motor Neuron Pathology in Amyotrophic Lateral Sclerosis by MRI: Towards Identifying Noninvasive Biomarkers of the Disease." Doctoral dissertation, Cleveland State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=csu1288020485

    Chicago Manual of Style (17th edition)

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© 2010, all rights reserved.
This open access ETD is published by Cleveland State University and OhioLINK.