Schneider, K.S.A.I.M; (2008) Electrophysiological biomarkers in genetic movement disorders. Doctoral thesis , UCL (University College London).

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Abstract

BACKGROUND. Neurodegenerative diseases are diseases of the nervous system with progressive course leading to death. Treatment remains symptomatic. Development of neuroprotective agents has been hampered for various reasons. This includes the inability of making the diagnosis accurately early in the course and the lack of reliable disease progression markers which could be used in future treatment trials. Transcranial magnetic stimulation (TMS) is a non-invasive and pain-free method for assessment of brain function. METHODS. Here we evaluated TMS and its potential of serving as reliable biomarker for neurodegenerative diseases with genetic cause. After clinical delineation of our patient cohorts with Huntington’s chorea and young-onset Parkin-related Parkinsonism, we enrolled both patients as well as asymptomatic/presymptomatic gene-carriers. Patients, carriers and age-matched healthy controls were studied using TMS to establish an electrophysiological footprint of these conditions. RESULTS. We found abnormalities in electrophysiological parameters which were present in manifesting patients and/or non-manifesting gene mutation carriers. In HD, both presymptomatic and early manifest patients had increased resting and active motor cortex thresholds. Short afferent inhibition (SAI), a measure of sensory-motor integration, was reduced in manifesting patients only. SAI changes were inversely correlated with clinical parameters like predicted year to onset and UHDRS motor score. Abnormalities in Parkin patients included prolonged central motor conduction time (CMCT), while thresholds and cortical inhibitory activity were normal. Asymptomatic carriers had increased motor thresholds and abnormal inhibitory measures (SICI recruitment) while CMCT was normal. CONCLUSION. We conclude that TMS may be a potential biomarker for neurodegenerative genetic diseases 1) to detect changes early in the disease course and to monitor disease progression; 2) to help differentiating between clinically similar diseases on the basis of certain electrophysiological patterns; and 3) to give insight into underlying mechanisms of the disorders studied. Our findings suggest the potential for future research.

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