Neurological deterioration in late infantile neuronal ceroid lipofuscinosis.
BACKGROUND
Late infantile neuronal ceroid lipofuscinosis (LINCL) is associated with progressive degeneration of the brain and retina starting in early childhood.


METHODS
Thirty-two individual neurologic, ophthalmologic, and CNS imaging (MRI and MRS) assessments of 18 children with LINCL were analyzed. Disease severity was followed by two rating scales, one previously established but modified to solely assess the brain and exclude the retinal disease (modified Hamburg LINCL scale), and a newly developed scale, with expanded evaluation of the CNS impairment (Weill Cornell LINCL scale).


RESULTS
For the 18 children, the Weill Cornell scale yielded a closer correlation with both age and time since initial clinical manifestation of the disease than did the modified Hamburg scale. There were no significant differences as a function of age or time since initial manifestation of the disease in the rating scales among the most frequent CLN2 mutations (G3556C, 56% of all alleles or C3670T, 22% of all alleles). Measurements of cortical MRS N-acetyl-aspartate content, MRI ventricular, gray matter and white matter volume, and cortical apparent diffusion coefficient correlated to a variable degree with the age of the children and the time since initial clinical manifestation of the disease. All imaging measurements correlated better with the Weill Cornell CNS scale compared to the modified Hamburg LINCL scale.


CONCLUSIONS
The data suggest that the Weill Cornell late infantile neuronal ceroid lipofuscinosis (LINCL) scale, together with several of the MRI measurements, may be useful in the assessment of severity and progression of LINCL and for the evaluation of novel therapeutic strategies.
Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. geneticmedicine@med.cornell.edu
S
S
Worgall
M V
MV
Kekatpure
L
L
Heier
D
D
Ballon
J P
JP
Dyke
D
D
Shungu
X
X
Mao
B
B
Kosofsky
M G
MG
Kaplitt
M M
MM
Souweidane
D
D
Sondhi
N R
NR
Hackett
C
C
Hollmann
R G
RG
Crystal
D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D000626:Aminopeptidases; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018450:Disease Progression; D010450:Endopeptidases / Q000235:genetics; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D009460:Neurologic Examination; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009887:Ophthalmoscopy; D009929:Organ Size; D017354:Point Mutation; D012160:Retina / Q000473:pathology; D057057:Serine Proteases; D012720:Severity of Illness Index; D035781:Siblings; D000091346:Tripeptidyl-Peptidase 1
D000091346:Tripeptidyl-Peptidase 1; D001224:Aspartic Acid; C000179:N-acetylaspartate; D010450:Endopeptidases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human