👤 Christoph Schwering

The neuronal ceroid lipofuscinoses (NCLs) are a group of disorders characterized by neurodegeneration and intracellular accumulation of an auto-fluorescent lipopigment. Together, NCLs represent the most common cause of cerebral neurodegenerative disease in children. CLN3 disease, the classic juvenile-onset form (JNCL) due to mutations in CLN3, is characterized by progressive vision loss, epilepsy, dementia, behavioral difficulties, and motor impairment. The Unified Batten Disease Rating Scale (UBDRS) is a disease-specific rating scale that was developed to assess disease severity in 4 domains: physical, behavior, seizures, and functional capability. Validity and reliability of the UBDRS has been established in a large North American cohort of over 130 individuals. The purpose of this study was to determine whether the UBDRS is valid and reliable when tested in an independent sample. Over the course of one week, 13 individuals with genetically confirmed CLN3 disease were evaluated with the UBDRS by 5 examiners at the University Medical Center Hamburg Eppendorf (UKE). One rater (JWM), one of the developers of the UBDRS, served as the reference standard. The other 4 raters were physicians with expertise in various forms of Batten Disease. After a formal training session, 13 individuals (age 16.5 ± 5.6 yrs) were evaluated simultaneous in parallel by the 5 raters. Inter-rater reliability of the Physical subscale was assessed with Intra-class Correlation (ICC) analysis. The relationship between age and severity was assessed and compared to previously published data from the North American cohort. The ICC among the 5 independent raters was 0.92, demonstrating excellent inter-rater reliability. The individual correlations of each UKE rater compared to the reference standard rater were all >0.95. The average UBDRS Physical Subscale score in this sample was 28 ± 21 (mean ± SD) with a range from 1 to 61. When evaluated as a function of participant age, the slope was 3.06 points/year (R We have shown excellent interrater reliability for the UBDRS as a clinical rating scale for CLN3 disease in a sample independent from previous work. The results of this study are comparable to those published by Kwon et al., 2011 in a North American cohort showing a slope of 2.86 points per year with a 95% CI of 2.27-3.45 (N = 82). Our results demonstrate excellence inter-rater reliability after training a new group of raters and provide additional evidence for construct validity of the UBDRS. The UBDRS is a valid and reliable rating scale that can used by trained raters to assess the severity and rate of progression of CLN3 disease. Show less

Juvenile CLN3 disease, the most prevalent form of Batten disease, is a progressive neurodegenerative disorder resulting from mutations in the CLN3 gene. The objective of this study was to design an ophthalmic rating scale for CLN3 disease in order to quantify disease progression. Retrospective, cross-sectional study. Patients underwent ophthalmic evaluations including visual testing, optical coherence tomography and fundus imaging. Patients were also assessed using the Hamburg Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) scoring system. Ophthalmic findings were divided into grades of severity ranging from 0 to 3, and the association between the extent of ocular disease and neurological function and age was assessed. Forty-two eyes of 21 patients were included. The mean age at the time of examination was 13.2 years (range, 5.3-21.9 years). The mean ophthalmic severity grade was 2.4 (range, 0-3). The mean neurological severity score was 9.9 (range, 4-14). Ophthalmic manifestations increased in severity with increasing age of the patients (r = -0.84; P < .001), and a strong correlation was found between the CLN3 ophthalmic rating scale score and the Hamburg JNCL score (r = 0.83; P < .001). Ophthalmic manifestations of CLN3 disease correlate closely with the severity of neurological symptoms and age of the patient. The newly established Hamburg CLN3 ophthalmic rating scale may serve as an objective marker of ocular disease severity and progression and may be valuable tool for the evaluation of novel therapeutic strategies for CLN3 disease. Show less