Thesis Format

Monograph

Chronic Neurological Impairment in Patients with Thrombotic Thrombocytopenic Purpura: Findings in Quantitative MRI

Jeffrey Hamilton, The University of Western OntarioFollow

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Huang, Susan S.H.

2nd Supervisor

Thiessen, Jonathan D.

Joint Supervisor

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening, microvascular blood disorder that affects approximately 5 people per million per year. The disorder is characterized by insufficient activity in ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13), which is an important enzyme in hemostasis because it prevents thrombosis. Along with blood clotting, other predominant symptoms are fever, anaemia, kidney failure, and neurological changes. Neurological changes may include confusion and decreased levels of consciousness, as well as depression and increased risk of seizures or stroke. However, little is known about the general pathology of these neurological changes and this forms the motivation for this research. An observational study using a comprehensive MRI protocol was evaluated in 13 patients and compared to results from assessments of depression and cognition. Despite prolonged remission, there is evidence of persistent neurocognitive decline as manifested in higher scores of depression and widespread white matter lesions.

Summary for Lay Audience

This project is driven by the poorly-understood neurological findings in the rare, life-threatening blood disorder called thrombotic thrombocytopenic purpura (TTP). The disorder is manifested by spontaneous blood clotting throughout the body. Other symptoms include fever and kidney failure. Furthermore, neurological impairment has been well-documented in the literature, but few studies have thoroughly investigated how the brain is affected as a result of TTP. Neurological impairment includes increased risk of having a stroke or a seizure, as well as depression and confusion. These persist despite the the most effective treatments.

This is an observational study to evaluate brain health over time in patients at various stages of the disorder from soon-after their first episode to remission to several years without relapse. The following thesis presents results from 13 patients at the first timepoint. Primary testing was conducted through a comprehensive, 65-minute magnetic resonance imaging (MRI) protocol. MRI is a widely-used imaging modality that offers great flexibility in the types of images that can be acquired. The acquistion includes five qualitative sequences, which are viewed by a neuroradiologist, and three novel, quantitative sequences. The principle quantitative imaging sequence in this thesis is called myelin water imaging (MWI). It is a technique to quantify myelin, one of the characteristic features of white matter. Secondary testing is conducted through online cognitive testing and a depression assessment completed in a clinical interview with a nurse. Both were completed as close to the date of the MRI scan as possible.

The objective of this thesis is to show and explain the differences between and within brains of patients with TTP using both qualitative MRI and MWI to quantify changes in brain white matter. Even though the sample size is small and there are no controls at this point in the longitudinal study, several interesting results are reported which help elucidate the poorly understood long-term impact of thrombotic thrombocytopenic purpura. These include higher scores of depression and widespread white matter damage.

Recommended Citation

Hamilton, Jeffrey, "Chronic Neurological Impairment in Patients with Thrombotic Thrombocytopenic Purpura: Findings in Quantitative MRI" (2020). Electronic Thesis and Dissertation Repository. 7566.
https://ir.lib.uwo.ca/etd/7566