Neuropsychological symptoms of juvenile-onset batten disease: experiences from 2 studies

Abstract

Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a progressive and fatal autosomal-recessive inherited lysosomal storage disorder of childhood. Core symptoms include vision loss, seizures, and mental and motor decline. This article presents data from 2 studies of neuropsychological function in juvenile neuronal ceroid lipofuscinosis. In the first cross-sectional pilot study, 15 children with genetic or clinicopathologic confirmation of juvenile neuronal ceroid lipofuscinosis completed a brief test of attention (mean age = 14.3 +/- 2.9 years, range = 8.75-18.74 years; 7 males, 8 females). Average attention performances were significantly below age-expected normative data. A second longitudinal study was then initiated to study neuropsychological function in greater depth, including change in function over time. The authors have enrolled 18 children to date (mean age = 12.88 +/- 3.59 years, range = 6.26-18.65; 11 males, 7 females). Of these, 5 children have completed a second (annual) re-evaluation. Results thus far indicate significant impairment in domains of auditory attention, memory, estimated verbal intellectual function, and verbal fluency. Neuropsychological impairment was significantly correlated with disease duration and with motor function as assessed by a disease-specific clinical neurologic rating scale. There was no significant difference between males and females in neuropsychological test performance. Neuropsychological function was worse among children with a positive seizure history. Juvenile neuronal ceroid lipofuscinosis-affected children exhibited significant and pervasive impairments on tests of auditory attention, verbal memory and repetition, verbal fluency, and an estimate of verbal intellectual ability. Preliminary follow-up data from an annual reassessment showed progressive declines in cognitive function, in particular on a task of working memory. Neuropsychological deficits are pervasive and progressive. Future research will focus on clarifying the relationship among disease duration, motor function, and neuropsychological performances, including the relative sensitivity of neuropsychological testing at different stages of motor impairment or disease duration.

Figure 1

Mean z scores across domains of neuropsychological function at first assessment.

Figure 2

Correlation of vocabulary score and disease duration in children with juvenile neuronal ceroid lipofuscinosis. R² = 0.696, P < .001. Ninety-five percent confidence intervals are shown.

Figure 3

(a) Bivariate scatter plot of motor function and neuropsychological function. Unified Batten Disease Rating Scale (UBDRS) motor score (median score; higher scores indicate worse function) and total neuropsychological score (age-corrected scaled scores; higher scores signify better function). At lower levels of cognitive function, there is a sharply linear association with the UBDRS motor score. At higher levels of cognitive function, motor function has greater variability. (b) Bivariate scatter plot of neurologists’ clinical impression of cognitive ability and neuropsychological function. (UBDRS cognitive score (median Clinical Global Impression score; higher scores indicate worse function) and total neuropsychological score (age-corrected scaled scores; higher scores signify better function).

Figure 4

Changes in cognitive test scores. *Score is constant across subjects; no error bar.

Figure 5

Digits Forward versus Digits Backward: patterns of change across 1 year. *Scores are constant across subjects; no error bars. LDSF = longest Digit Span Forward (scaled score); LDSB = longest Digit Span Backward (scaled score); DSF Raw = raw number of digits recalled on Digits Forward; DSB Raw = raw number of digits recalled on Digits Backward.