會議議程

Executive Summary：
Dr. Kuan-Lin Lai graduated from National Yang-Ming University in Taipei, Taiwan, in 2002, and completed his neurology residency at Taipei Veterans General Hospital. Since 2006, he has served as an attending physician and neurological consultant. Dr. Lai specializes in peripheral neuropathies and clinical neurophysiological assessment. From 2021 to 2023, Dr. Lai held the position of Section Director for the Peripheral Nervous System at the Taiwan Neurological Society.

Lecture Abstract：
Paraproteins, or monoclonal immunoglobulins, are markers of clonal B-cell or plasma cell dyscrasias that frequently exert pathogenic effects on the peripheral nervous system. Paraprotein-related neuropathy presents a formidable "diagnostic maze" due to its broad clinical spectrum, ranging from indolent sensory-predominant polyneuropathy to aggressive, demyelinating, or multifocal syndromes. The clinical heterogeneity often leads to diagnostic overlap with common immune-mediated neuropathies, such as CIDP.

Precise diagnosis hinges on identifying red-flag features, including disproportionate sensory ataxia, distal accentuation of conduction slowing, and specific paraprotein-isotype associations (e.g., IgM anti-MAG activity). Clinicians must distinguish incidental monoclonal gammopathy from truly pathogenic paraproteinemias through a meticulous integration of electrophysiology, immunofixation electrophoresis, and, when indicated, bone marrow biopsy or even nerve biopsy evaluation. This presentation will provide a structured diagnostic algorithm to differentiate these entities, highlight the significance of subtle hematologic clues, and discuss the implications for targeted immunotherapy. Mastering this intersection of neurology and hematology is essential for timely intervention and optimizing patient outcomes.

Executive Summary：
Dr. Keita Takahashi is a Lecturer in the Department of Neurology and Stroke Medicine at Yokohama City University Hospital, Japan. He received his M.D. from Kyorin University School of Medicine in 2008 and earned his Ph.D. in Neurology from Yokohama City University in 2015. Since joining Yokohama City University, he has built a distinguished career in neurology, with particular expertise in neuroimmunology, spinal muscular atrophy, and biomarker development.

Dr. Takahashi has received several prestigious awards, including the Japan Multiple Sclerosis Society Medical Research Grant, the Outstanding Thesis Award from Yokohama City University, and the President’s Award for Best Presentation at the Multiple Sclerosis Summer College.

His research has focused on the role of LOTUS (lateral olfactory tract usher substance) as a biomarker and therapeutic target in neuroinflammatory and neurodegenerative diseases. He was among the first to report that cerebrospinal fluid LOTUS levels are associated with disease activity in multiple sclerosis. His work has also demonstrated therapeutic potential for LOTUS in amyotrophic lateral sclerosis models.

More recently, Dr. Takahashi has been actively involved in research on adult spinal muscular atrophy, particularly regarding the long-term efficacy of nusinersen and the impact of dosing intervals in adult patients. His work aims to optimize treatment strategies for patients with severe neurological diseases.

Lecture Abstract：
Spinal Muscular Atrophy is a progressive and intractable lower motor neuron disease characterized by muscle atrophy and weakness resulting from degeneration of anterior horn cells in the spinal cord. In recent years, treatment with Nusinersen has become available, and marked therapeutic benefits have been reported in pediatric patients. Although a certain degree of efficacy has also been demonstrated in adult patients, it has become increasingly clear that sufficient improvement in motor function is not always achieved, particularly in patients with more severe disability. Therefore, establishing an optimal treatment strategy tailored to each patient is increasingly important.

Interestingly, maintenance dosing of nusinersen in Japan is administered every six months, which differs from the four-month interval adopted in most major countries, resulting in a lower treatment frequency and lower annual cumulative dose. Therefore, we compared treatment outcomes of nusinersen in adult SMA patients between Japan and Europe to evaluate the impact of differences in dose and dosing frequency on therapeutic efficacy.

As a result, adult ambulatory patients showed sufficient therapeutic benefit even with the Japanese six-month dosing interval. In contrast, among non-ambulatory adult patients, some improvement was observed during the loading phase; however, the degree of improvement during the maintenance phase was less pronounced than that reported in European cohorts receiving four-month dosing intervals. These findings suggest that the therapeutic efficacy of nusinersen may depend on differences in both dose and dosing frequency.

In this section, based on Japanese data and current evidence, including the ongoing DEVOTE trial evaluating high-dose nusinersen therapy, we would like to discuss the optimal treatment strategy for adult SMA patients.