Development, Application, and Mechanistic Investigation of a Novel Minimally-Invasive Bidirectional Epidural Cerebellar Stimulation Technique for Cerebellar Cognitive Affective Syndrome

Development, Application, and Mechanistic Investigation of a Novel Minimally-Invasive Bidirectional Epidural Cerebellar Stimulation Technique for Cerebellar Cognitive Affective Syndrome

Building on previous findings regarding microglial immune function and the immunosuppressive effects of glucocorticoids, this project centers on the cerebellum's role in cognitive science. Using Cushing's syndrome-induced cerebellar atrophy leading to CCAS as a model, we aim to elucidate the pathogenic mechanisms governed by the neuro-adrenal-immune network and to uncover the molecular basis by which a novel minimally invasive brain-machine fusion system ameliorates cerebellar ataxia and cognitive impairment.

Inclusion Criteria:

• 1. Clinically and biochemically confirmed ACTH-dependent or ACTH-independent Cushing syndrome (loss of serum cortisol circadian rhythm, elevated 24-hour urinary free cortisol, and failure to suppress on low-dose dexamethasone suppression test).

  2. Cranial MRI demonstrating unequivocal cerebellar atrophy (CCAS imaging criterion: cerebellar hemisphere or vermian volume ≥1.5 SD below age-matched normative data).

  3. Established clinical diagnosis of CCAS (meets Schmahmann criteria, CCAS-S total score ≥20).

  4. Cerebellar ataxia rating scale (SARATA) ≥10, indicating at least moderate motor ataxia.

  5. Positive cognitive impairment screen (MoCA <26, or Z-scores ≤-1.5 in at least two cognitive domains).

  6. Willingness to undergo minimally invasive epidural cerebellar stimulation and provision of written informed consent.

Exclusion Criteria:

Patients with significant systemic disease; occurrence of major complications or irreproducible, critical deviations in data collection or experimental procedures; or any circumstance rendering continued participation inappropriate-including clinical deterioration, serious adverse events, or poor compliance-will result in discontinuation of the subject's enrollment.