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

Margaux C Masten; Justin D Williams; Jennifer Vermilion; Heather R Adams; Amy Vierhile; Alyssa Collins; Frederick J Marshall; Erika F Augustine; Jonathan W Mink

doi:10.1212/WNL.0000000000009454

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.

Authors

Margaux C Masten¹, Justin D Williams², Jennifer Vermilion², Heather R Adams², Amy Vierhile², Alyssa Collins², Frederick J Marshall², Erika F Augustine², Jonathan W Mink²

Affiliations

¹ From the Departments of Neurology (M.C.M., J.D.W., J.V., H.R.A., A.V., A.C., F.J.M., E.F.A., J.W.M.), Neuroscience (J.W.M.), and Pediatrics (J.V., H.R.A., E.F.A., J.W.M.) and Center for Health and Technology (E.F.A.), University of Rochester School of Medicine and Dentistry; and University of Rochester School of Nursing (A.V.), NY. margaux_masten@urmc.rochester.edu.
² From the Departments of Neurology (M.C.M., J.D.W., J.V., H.R.A., A.V., A.C., F.J.M., E.F.A., J.W.M.), Neuroscience (J.W.M.), and Pediatrics (J.V., H.R.A., E.F.A., J.W.M.) and Center for Health and Technology (E.F.A.), University of Rochester School of Medicine and Dentistry; and University of Rochester School of Nursing (A.V.), NY.

Abstract

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

Substances

CLN3 protein, human
Membrane Glycoproteins
Molecular Chaperones

Abstract

Publication types

MeSH terms

Substances

Grants and funding