Neurological deterioration in late infantile neuronal ceroid lipofuscinosis

S. Worgall, M. V. Kekatpure, L. Heier, D. Ballon, J. P. Dyke, D. Shungu, X. Mao, B. Kosofsky, M. G. Kaplitt, M. M. Souweidane, D. Sondhi, N. R. Hackett, C. Hollmann, Ronald Crystal

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)521-535
Number of pages15
JournalNeurology
Volume69
Issue number6
DOIs
Publication statusPublished - 1 Aug 2007
Externally publishedYes

Fingerprint

Neuronal Ceroid-Lipofuscinoses
Alleles
Retinal Diseases
Brain
Nervous System
Retina
Mutation

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Worgall, S., Kekatpure, M. V., Heier, L., Ballon, D., Dyke, J. P., Shungu, D., ... Crystal, R. (2007). Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology, 69(6), 521-535. https://doi.org/10.1212/01.wnl.0000267885.47092.40

Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. / Worgall, S.; Kekatpure, M. V.; Heier, L.; Ballon, D.; Dyke, J. P.; Shungu, D.; Mao, X.; Kosofsky, B.; Kaplitt, M. G.; Souweidane, M. M.; Sondhi, D.; Hackett, N. R.; Hollmann, C.; Crystal, Ronald.

In: Neurology, Vol. 69, No. 6, 01.08.2007, p. 521-535.

Research output: Contribution to journalArticle

Worgall, S, Kekatpure, MV, Heier, L, Ballon, D, Dyke, JP, Shungu, D, Mao, X, Kosofsky, B, Kaplitt, MG, Souweidane, MM, Sondhi, D, Hackett, NR, Hollmann, C & Crystal, R 2007, 'Neurological deterioration in late infantile neuronal ceroid lipofuscinosis', Neurology, vol. 69, no. 6, pp. 521-535. https://doi.org/10.1212/01.wnl.0000267885.47092.40
Worgall S, Kekatpure MV, Heier L, Ballon D, Dyke JP, Shungu D et al. Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology. 2007 Aug 1;69(6):521-535. https://doi.org/10.1212/01.wnl.0000267885.47092.40
Worgall, S. ; Kekatpure, M. V. ; Heier, L. ; Ballon, D. ; Dyke, J. P. ; Shungu, D. ; Mao, X. ; Kosofsky, B. ; Kaplitt, M. G. ; Souweidane, M. M. ; Sondhi, D. ; Hackett, N. R. ; Hollmann, C. ; Crystal, Ronald. / Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. In: Neurology. 2007 ; Vol. 69, No. 6. pp. 521-535.
@article{4957bc13f9d54f2194bb7e625c23796b,
title = "Neurological deterioration in late infantile neuronal ceroid lipofuscinosis",
abstract = "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.",
author = "S. Worgall and Kekatpure, {M. V.} and L. Heier and D. Ballon and Dyke, {J. P.} and D. Shungu and X. Mao and B. Kosofsky and Kaplitt, {M. G.} and Souweidane, {M. M.} and D. Sondhi and Hackett, {N. R.} and C. Hollmann and Ronald Crystal",
year = "2007",
month = "8",
day = "1",
doi = "10.1212/01.wnl.0000267885.47092.40",
language = "English",
volume = "69",
pages = "521--535",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Neurological deterioration in late infantile neuronal ceroid lipofuscinosis

AU - Worgall, S.

AU - Kekatpure, M. V.

AU - Heier, L.

AU - Ballon, D.

AU - Dyke, J. P.

AU - Shungu, D.

AU - Mao, X.

AU - Kosofsky, B.

AU - Kaplitt, M. G.

AU - Souweidane, M. M.

AU - Sondhi, D.

AU - Hackett, N. R.

AU - Hollmann, C.

AU - Crystal, Ronald

PY - 2007/8/1

Y1 - 2007/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34548392810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548392810&partnerID=8YFLogxK

U2 - 10.1212/01.wnl.0000267885.47092.40

DO - 10.1212/01.wnl.0000267885.47092.40

M3 - Article

VL - 69

SP - 521

EP - 535

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 6

ER -