Motor function impairment is an early sign of CLN3 disease

Willemijn F E Kuper; Claudia van Alfen; Linda van Eck; Barbara C H Huijgen; Edward E S Nieuwenhuis; Marco van Brussel; Peter M van Hasselt

doi:10.1212/WNL.0000000000007773

Motor function impairment is an early sign of CLN3 disease

Neurology. 2019 Jul 16;93(3):e293-e297. doi: 10.1212/WNL.0000000000007773. Epub 2019 Jun 10.

Authors

Willemijn F E Kuper¹, Claudia van Alfen¹, Linda van Eck¹, Barbara C H Huijgen¹, Edward E S Nieuwenhuis¹, Marco van Brussel¹, Peter M van Hasselt²

Affiliations

¹ From the Departments of Metabolic Diseases (W.F.E.K., P.M.v.H.), Pediatric Gastroenterology (E.E.S.N.), and Medical Physiology, Child Development and Exercise Center (M.v.B.), Wilhelmina Children's Hospital, University Medical Center Utrecht; Bartiméus Institute for the Visually Impaired (C.v.A., L.v.E.), Zeist and Doorn; and Center for Human Movement Sciences (B.C.H.H.), University Medical Center Groningen, University of Groningen, the Netherlands.
² From the Departments of Metabolic Diseases (W.F.E.K., P.M.v.H.), Pediatric Gastroenterology (E.E.S.N.), and Medical Physiology, Child Development and Exercise Center (M.v.B.), Wilhelmina Children's Hospital, University Medical Center Utrecht; Bartiméus Institute for the Visually Impaired (C.v.A., L.v.E.), Zeist and Doorn; and Center for Human Movement Sciences (B.C.H.H.), University Medical Center Groningen, University of Groningen, the Netherlands. p.vanhasselt@umcutrecht.nl.

PMID: 31182507
DOI: 10.1212/WNL.0000000000007773

Abstract

Objective: To delineate timing of motor decline in CLN3 disease.

Methods: Motor function, assessed by the 6-Minute Walk Test (6MWT), was evaluated repeatedly in 15 patients with CLN3 disease, resulting in 65 test results and during one occasion in 2 control cohorts. One control cohort (n = 14) had isolated visual impairment; a second cohort (n = 12) exhibited visual impairment in combination with neurologic impairments. Based on 6MWT reference values in healthy sighted children, z scores of 6MWT results in patients with CLN3 disease and control cohort individuals were calculated. 6MWT results were correlated with age-including multilevel modeling analysis allowing assessment of imbalanced repeated measurements-and with Unified Batten Disease Rating Scale (UBDRS) scores.

Results: In CLN3 disease, 6MWT scores were already impaired from first testing near diagnosis (mean z scores of -3.6 and -4.7 at 7 and 8 years of age, respectively). Afterwards, 6MWT scores continuously declined with age (r = -0.64, p < 0.0001) and with increasing UBDRS scores (r = -0.60, p = 0.0001), confirming correlation with disease progression. The decrease was more pronounced at a later age, as shown by the nonlinear multilevel model for 6MWT results in CLN3 disease (y = 409.18 - [0.52 × age²]). In contrast, an upward trend of 6MWT scores with age was observed in the control cohort with isolated visual impairment (r = 0.56; p = 0.04) similar to healthy, sighted children. The control cohort with additional neurologic impairments displayed a slightly decreased 6MWT walking distance independent of age.

Conclusions: The 6MWT unveils early onset of motor decline in CLN3 disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Case-Control Studies
Child
Child, Preschool
Disease Progression
Female
Humans
Male
Neuronal Ceroid-Lipofuscinoses / physiopathology*
Physical Functional Performance
Vision Disorders
Walk Test*
Young Adult