Neuropsychological symptoms of juvenile-onset batten disease: experiences from 2 studies.
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.
Adams
Heather R
HR
University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. heather_adams@urmc.rochester.edu
Kwon
Jennifer
J
Marshall
Frederick J
FJ
de Blieck
Elisabeth A
EA
Pearce
David A
DA
Mink
Jonathan W
JW
D000293:Adolescent; D000328:Adult; D001288:Attention / Q000502:physiology; D002648:Child; D003072:Cognition Disorders / Q000209:etiology; D002658:Developmental Disabilities / Q000209:etiology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D001523:Mental Disorders / Q000209:etiology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000503:physiopathology* / Q000523:psychology*; D009483:Neuropsychological Tests
Epilepsia. 1999 Jun;40(6):796-9
10368082
Curr Opin Neurol. 1999 Apr;12(2):167-76
10226749
Mol Genet Metab. 1999 Apr;66(4):231-3
10191106
Dev Med Child Neurol. 2006 Apr;48(4):259-64
16542512
Neurology. 2005 Jul 26;65(2):275-9
16043799
J Neurosci Res. 2005 Mar 1;79(5):573-83
15657902
J Intellect Disabil Res. 2005 Jan;49(Pt 1):25-32
15634309
Blood. 1996 Jun 1;87(11):4894-902
8639864
J Mol Diagn. 2004 Aug;6(3):260-3
15269304
J Intellect Disabil Res. 2001 Feb;45(Pt 1):8-17
11168772
Neurol Sci. 2000;21(3 Suppl):S35-41
11073226
Am J Hum Genet. 1997 Aug;61(2):310-6
9311735
J Inherit Metab Dis. 1995;18(4):413-29
7494400
Dev Med Child Neurol. 1983 Oct;25(5):588-90
6354796
Dev Med Child Neurol. 1973 Jun;15(3):313-23
4718684
Curr Opin Hematol. 1999 Nov;6(6):377-82
10546790