Gargoylism (Hurler's Disease): A Neuropathological Report

Naidoo, D.

doi:10.1192/bjp.99.414.74

Cited by 24 publications

(3 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, glycosaminoglycans are not directly toxic, and the cause of neurological deterioration in children with MPS I is not presently clear. Brain histological findings in MPS I patients have shown neuronal cell loss, gliosis, swelling of cell bodies and dendrites, prominent perivascular (i.e., Virchow-Robin) spaces, leptomeningeal thickening, and gross atrophy (Naidoo, 1953). In addition, brain MR imaging findings show hydrocephalus, cribriform changes, and hyperintense lesions of white matter (Seto et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

Provenzale

Nestrašil

Chen

et al. 2015

Experimental Neurology

View full text Add to dashboard Cite

Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-l-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-l-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

Provenzale

Nestrašil

Chen

et al. 2015

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…These alterations occurred in mice aged 5 months, in a mixed‐gender cohort, and were confirmed by RT‐PCR. Myelination delay has been reported on magnetic resonance imaging of human participants with MPS types I and II (Lee et al, 1993), and autopsies have shown patchy areas of demyelination and some, albeit inconsistent, lipid abnormalities in the brain (Clausen et al, 1967; Constantopoulos et al, 1980; Constantopoulos and Dekaban, 1978; Nagashima et al, 1976; Naidoo, 1953) including increased amounts of cholesterol, phospholipid, gangliosides (GM2, GM3, and GD3), ceramide dihexoside in a patient with the severe (Hurler) form of MPS I (Constantopoulos et al, 1980). Savile and colleagues found elevations in the glycerophospholipid bis(monoacylglycero)phosphate in several regions of the brain of MPS I mice, and dietary manipulation of fatty acid intake altered performance of the mice (mixed gender) on behavioral testing (Saville et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Myelin and Lipid Composition of the Corpus Callosum in Mucopolysaccharidosis Type I Mice

Nestrašil

Kan

et al. 2020

Lipids

View full text Add to dashboard Cite

Mucopolysaccharidosis type I (MPS I) is a lysosomal disease with progressive central nervous system involvement. This study examined the lipid, cholesterol, and myelin basic protein composition of white matter in the corpus callosum of MPS I mice. We studied 50 week-old, male MPS I mice and littermate, heterozygote controls (n = 12 per group). Male MPS I mice showed lower phosphatidylcholine and ether-linked phosphatidylcholine quantities than controls (p < 0.05). Twenty-two phospholipid or ceramide species showed significant differences in percent of total. Regarding specific lipid species, MPS I mice exhibited lower quantities of sphingomyelin 18:1, phosphatidylserine 38:3, and hexosylceramide d18:1(22:1) mH 2 O than controls. Principal components analyses of polar, ceramide, and hexosylceramide lipids, respectively, showed some separation of MPS I and control mice. We found no significant differences in myelin gene expression, myelin basic protein, or total cholesterol in the MPS I mice versus heterozygous controls. There was a trend toward lower proteolipid protein-1 levels in MPS I mice (p = 0.06). MPS I mice show subtle changes in white matter composition, with an unknown impact on pathogenesis in this model.

show abstract

“…This emphasis on the biochemical changes has led to relative neglect of the morphological aspect, though Green (1948), Jervis (1950), Henderson (1952), Naidoo (1953, Dawson (1954), and Bishton et al (1955) have described histological studies of the brains of gargoyles in some detail, and several other case reports are also on record (Wallace et al, 1966, andDekaban et al, 1971). The ultrastructural changes seen in biopsy material from the central nervous system were first reported by Aleu et al (1965), and further studies have been made by Wallace et al (1966) and by Loeb et al (1968).…”

mentioning

confidence: 99%

The cerebellum in mucopolysaccharidosis: A histological, histochemical, and ultrastructural study

Doshi¹,

Sandry²,

Churchill³

et al. 1974

Journal of Neurology, Neurosurgery & Psychiatry

View full text Add to dashboard Cite

SYNOPSIS Studies in the morphology, histochemistry, and ultrastructure of the cerebellum, with special reference to the Purkinje cell dendrites, have been undertaken in eight cases of gargoylism. The results suggest that the demonstration of ovoid swellings of the Purkinje cell dendrites by the Cajal method for the cerebellum, together with certain histochemical findings, may enable a diagnosis of mucopolysaccharidosis to be made. Possible mechanisms for the formation of these swellings are briefly discussed.

show abstract

Gargoylism (Hurler's Disease): A Neuropathological Report

Abstract: Hurler's disease is characterized by chondro-dystrophic skeletal changes, corneal opacities, hepatosplenomegaly and mental defect. The skeletal changes are such that the patient presents a large head, grotesque facies, deformed limbs and kyphosis.

Cited by 24 publications

References 13 publications

Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

Myelin and Lipid Composition of the Corpus Callosum in Mucopolysaccharidosis Type I Mice

The cerebellum in mucopolysaccharidosis: A histological, histochemical, and ultrastructural study

Contact Info

Product

Resources

About