Case Series of 46 Patients With Nonketotic Hyperglycemia-associated Chorea: A Retrospective Follow-up Study.

Abstract

Nonketotic hyperglycemia-associated chorea (NKHC) is a rare but underrecognized complication of diabetes mellitus, with an unclear pathogenesis and variable clinical presentations. Recent studies highlight the role of metabolic disturbances and cerebrovascular pathophysiology in its development. To investigate the clinical, imaging, and therapeutic characteristics of 46 patients with NKHC, integrating multimodal neuroimaging and long-term follow-up data from 2013 to 2022. This multicenter retrospective study enrolled patients with acute-onset hemichorea/hemiballismus, nonketotic hyperglycemia (random blood glucose ≥11.1 mmol/L), and basal ganglia abnormalities on magnetic resonance imaging (MRI). Clinical outcomes, metabolic profiles, and neuroimaging features (including T1-weighted hyperintensity, dynamic contrast-enhanced-MRI, and magnetic resonance spectroscopy) were systematically analyzed. The cohort exhibited a mean age of 68.6 ± 10.4 years (range 48-89), with equal sex distribution. Hyperglycemia (mean glycated hemoglobin 11.4% ± 3.8%) and T1-weighted hyperintensity in the contralateral basal ganglia were universal (91.3% on MRI). Notably, 26.1% of patients presented with normoglycemia at admission yet exhibited typical chorea, challenging the "hyperglycemia-first" paradigm. Follow-up MRI revealed dynamic changes in T1 signal intensity, with 2 cases demonstrating symptom exacerbation despite signal resolution. NKHC manifests heterogeneous clinical and imaging phenotypes, suggesting a multifactorial pathogenesis involving metabolic derangement, cerebrovascular insufficiency, and blood-brain barrier disruption. Normoglycemic presentations and paradoxical imaging changes warrant further mechanistic exploration. To our knowledge, this study represents the largest case series of NKHC to date, offering valuable insights into the clinical and imaging characteristics of this condition.