Neurophysiological Insights into the Pathophysiology of Stiff‐Person Spectrum Disorders

Moura, João;Rocchi, Lorenzo

Second

Writing - Review & Editing

;Zandi, Michael;Balint, Bettina;Bhatia, Kailash P.;Latorre, Anna

2025-01-01

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Abstract

Background: Stiff Person Spectrum Disorders (SPSD) are classically defined by the presence of muscle stiffness, spasms and hyperactivity of the central nervous system. There is a notable correlation between neurophysiological features and the clinical hallmark of SPSD, which has greatly encouraged the use of these techniques for diagnostic purposes. Besides, electrophysiological techniques allow for a functional evaluation of the ‘hyperactivity of the CNS’, thus offering the opportunity to clarify the mechanisms underlying this disorder. This review delves into the current knowledge on the electrophysiological aspects of SPSD, highlighting the pivotal role of various studies in unravelling its pathophysiology. Methods: Literature review for studies on SPSD that included a neurophysiological evaluation. Results: We first examined the abnormal neurophysiological findings of SPSD across the central nervous system, from the spinal circuit to the motor cortex. Subsequently, we discussed their pathological implications and explored how these findings can be interpreted within the framework of an immune-mediated disorder. Conclusions: Two primary questions remain unanswered: the localization of the primary abnormality within the central nervous system and the connection between the autoimmune basis of SPSD and its neurophysiological aspects. Addressing these questions could provide invaluable insights into SPSD etiology and targeted therapeutic strategies.