Program

Executive Summary：
Dr Sung-Tsang Hsieh graduated from National Taiwan University for his MD and completed neurology resident training at National Taiwan University Hospital. He got Neuroscience PhD at Johns Hopkins University and did postdoc at Neurology of Johns Hopkins Hospital. Currently Dr Hsieh is an attending neurologist at National Taiwan University Hospital and holds professorship at Department of Anatomy and Cell Biology of National Taiwan University. Dr Hsieh is a pioneer in developing skin biopsy and quantifying skin nerves as a pathologic signature of small-diameter nociceptive nerve degeneration. This skin biopsy approach has become the gold standard to diagnose small fiber neuropathy. With this achievement, he is one of the members in the Skin Biopsy Task Force of European Federation of Neurological Societies and was elected as a Fellow of American Academy of Neurology. Since pain due to small fiber neuropathy is potentially attributed to maladaptive brain responses, over the last decade, Dr Hsieh and his team have developed integrated assessment system of small fiber neuropathy incorporating quantitative sensory testing, contact heat evoked potential (CHEP), and heat-activated functional MRI. Hereditary transthyreting amyloidosis (ATTRv) is one of the etiologies causing small fiber neuropathy and autonomic dysfunction and Dr Hsieh’s group identified a unique genotype of transthyretin (TTR) A97S as the major etiology of Taiwanese with ATTRv. Furthermore, Dr Hsieh and colleagues established the first brain bank in Taiwan to investigate the mechanisms and therapeutic targets of rare disease and neurodegneration.

Lecture Abstract：
Small fiber neuropathy, a unique type of peripheral nerve disorder, mainly affects small-diameter sensory nerves which are responsible for thermal and nociceptive functions. In small fiber neuropathy, there are two major manifestations: (1) negative symptoms, i.e. a loss of function, such as insensibility to noxious stimulus resulting in painless wounds and (2) positive symptoms, i.e. enhanced excitability of the neural axis causing neuropathic pain. During the last decade, we witnessed tremendous progress in the diagnosis of small fiber neuropathy and elucidation of the mechanisms of neuropathic pain in the context of (1) pathology: skin biopsy, (2) psychophysics: quantitative sensory testing (QST), (3) physiology: contact heat evoked potential (CHEP), laser evoked potential (LEP), and pain-related evoked potential (PREP), and (4) neuroimaging: functional MRI (fMRI), diffusion tensor imaging (DTI), connectome study). Small fibers are difficult to visualize under light microscopy and hence the diagnosis and confirmation of small-diameter nerve degeneration. The technique of punch skin biopsy together with sensitive immunohistochemistry and quantification of intraepidermal nerve fiber density (IENFd) provides objective and quantitative evidence of pathology for small fiber degeneration. Thermal thresholds measured by QST reflect functional capacity of small fibers. Noxious stimuli evoked potential including CHEP, LEP, and PREP offers physiological signatures of small fibers from different perspectives. Although small fiber neuropathy is a peripheral nerve degenerative disorder, peripheral sensitization could not fully account for the mechanism of neuropathic pain. We applied neuroimaging approaches including various sequencing and algorithms of resting-state and task-activated fMRI, structural connectome, and network analysis demonstrated concomitant central mechanism of maladaptive brain plasticity underlying neuropathic pain after nociceptive nerve degeneration. These observations lay down the foundations for designing medications and neuromodulation to treat the positive symptoms of neuropathic pain in small fiber neuropathy.