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. Conclusion: 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.