The CLN3 Disease Staging System: A new tool for clinical research in Batten disease

Neurology. 2020 Jun 9;94(23):e2436-e2440. doi: 10.1212/WNL.0000000000009454. Epub 2020 Apr 16.


Objective: To develop a disease-specific staging system for CLN3 disease and to test the hypothesis that salient and discrete clinical features of CLN3 disease may be used to define disease stages by analyzed data from an 18-year-long natural history study.

Methods: A proposed staging system, the CLN3 Staging System (CLN3SS), was based on salient and clinically meaningful endpoints. The relationships between stage and age, stage and Unified Batten Disease Rating Scale (UBDRS) physical severity score, and stage and UBDRS capability impairment subscale scores were determined. We used t tests to determine whether the stages were significantly different from each other on the basis of age and scores.

Results: Data were analyzed from 322 evaluations in 108 individuals. There were significant differences among the stages based on age and severity scores. For individuals with longitudinal data, no individual reverted to a less severe stage over time.

Conclusion: The CLN3SS is a disease-specific staging system that can be used to classify individuals into specific strata based on age and disease severity. The CLN3SS has potential applications in clinical trials for cohort stratification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Gait Disorders, Neurologic / etiology
  • Humans
  • Male
  • Membrane Glycoproteins / deficiency
  • Molecular Chaperones
  • Neuronal Ceroid-Lipofuscinoses / complications
  • Neuronal Ceroid-Lipofuscinoses / diagnosis*
  • Prognosis
  • Seizures / etiology
  • Severity of Illness Index
  • Vision Disorders / etiology


  • CLN3 protein, human
  • Membrane Glycoproteins
  • Molecular Chaperones