Neuropathology of Various Types of Niemann-Pick Disease

Elleder, M; Jirasek, Adam

doi:10.1007/978-3-642-81553-9_60

Cited by 28 publications

(8 citation statements)

References 14 publications

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“…In addition, neuroaxonal dystrophy (dystrophic axons) is uniquely frequent in the NPC brain ( Fig. 2), as emphasized by Elleder and Jirasek (22,23). More recently an association of neurofibrillary tangles (NFTS) and neuropil threads has been recognized in the brain of NPC cases with a slow- ly progressive course (16,46,82).…”

Section: Pathologymentioning

confidence: 79%

Recent Advances in Elucidating Niemann‐Pick C Disease

1998

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Lysosomal sequestration of endocytosed LDL‐derived cholesterol, premature and abnormal enrichment of cholesterol in trans Golgi cisternae and accompanying anomalies in intracellular sterol trafficking are the hallmark phenotypic features of the Niemann‐Pick C (NPC) lesion. A variable severity of these alterations has been observed, with only partial correlation between clinical and biochemical phenotypes. NPC also affects the metabolism of sphingolipids, and other biochemical abnormalities have been reported. Occurrence of neurofibrillary tangles in the brain of patients with a slowly progressive course is a recent intriguing observation. Genetic heterogeneity was established by cell hybridization and linkage studies. The two complementation groups could not be distinguished from each other by clinical, cellular or biochemical criteria, suggesting that the two gene products may interact or function sequentially. The major (> 90% of patients) NPC1 gene was mapped to 18q11 and recently isolated by positional cloning. The cDNA sequence predicts a 1278‐amino acid protein, with 13 to 16 possible transmembrane regions and a putative cholesterol‐sensing domain. Two murine models of the disease involving the same gene are known. The murine cDNA and the npcnih mutation have been characterized. Described homologies of the NPC1 protein are in line with its putative involvement in cellular cholesterol traffic.

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Section: Pathologymentioning

confidence: 79%

Recent Advances in Elucidating Niemann‐Pick C Disease

1998

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“…[19][20][21] The earliest human neuropathologic studies showed that neuroaxonal dystrophy was maximal in the thalamus and cerebellum. 22 In humans, neuropathologic studies demonstrated that noncerebellar brain regions develop NFTs in the basal ganglia, thalamus, brain stem, cerebral cortex, and hippocampus. 7,23,24 The convergent animal and human data suggest that in addition to notable cerebellar Purkinje cell loss, significant changes also occur in the thalamus and hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Subcortical Volumetric Reductions in Adult Niemann-Pick Disease Type C: A Cross-Sectional Study

Walterfang

Patenaude

Abel³

et al. 2012

AJNR Am J Neuroradiol

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“…The Purkinje cells of the cerebellum are particularly sensitive to the accumulation of GM2 and GM3 gangliosides that are a feature of NPC [29,30]. Additionally, at least one specific NPC1 mutation with unusually rapid adolescent-onset clinical course is associated with severe and early atrophy in the cerebellar vermis [31].…”

Section: Discussionmentioning

confidence: 97%

Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann–Pick disease type C patients treated with miglustat

et al. 2015

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Niemann-Pick disease type C (NPC) is a rare neurovisceral disorder resulting in impaired intracellular lipid trafficking. The only disease-modifying treatment available to date is miglustat, an iminosugar inhibiting the accumulation of lipid by-products in neurons. This study explored how changes in cerebellar grey and white matter volumes, and in subcortical volumes, related to patient treatment status and disability and ataxia ratings. Nine adult-onset NPC patients and 17 matched controls underwent T1-weighted MRI. One patient was not receiving miglustat, and pre-treatment data were available for a further patient. Semi-automated cerebellar and subcortical segmentation was undertaken, and the rates of change in putamen, hippocampal, thalamic and caudal volumes, and grey and white matter cerebellar volumes, were compared to rates of change in Iturriaga disability score, Brief Ataxia Rating Scale (BARS), and horizontal saccadic gain. Untreated NPC patients appeared to lose cerebellar grey and white matter, bilateral thalamic volume, and right caudate volume faster than treated patients. Cerebellar grey matter volume loss and volume loss in the left thalamus were significantly correlated with Iturriaga disability scale changes. Change in both cerebellar grey and white matter was correlated with decrease in horizontal saccadic gain, but not with change in BARS. This is the first study to examine longitudinal treatment effects of miglustat on cerebellar and subcortical volumes in patients with adult-onset NPC, and is evidence that miglustat may have a protective effect on cerebellar and subcortical structure and function.

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Neuropathology of Various Types of Niemann-Pick Disease

Cited by 28 publications

References 14 publications

Recent Advances in Elucidating Niemann‐Pick C Disease

Recent Advances in Elucidating Niemann‐Pick C Disease

Subcortical Volumetric Reductions in Adult Niemann-Pick Disease Type C: A Cross-Sectional Study

Longitudinal changes in cerebellar and subcortical volumes in adult-onset Niemann–Pick disease type C patients treated with miglustat

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