Infantile neuroaxonal dystrophy

Hedley‐Whyte, E. Tessa; Fh, Gilles; Bg, Uzman

doi:10.1212/wnl.18.9.891

Cited by 77 publications

(12 citation statements)

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“…An inverse relationship is possible and it may not be excluded that the VTS are in fact malformations of the SV. This is also suggested by H arman et al [1969] and others [Mugniani et al, 1967;Ramsey, 1967;G onatas et al, 1967a], Only swellings of type 1 show morphological similarities with changes observed in other diseases or experimental conditions, such as experi mental vitamin E deficiency [Pentschew et al, 1962;Lampert et al, 1964aLampert et al, , 1964b, INAD [Herman et al, 1969;Hedley-White et al, 1968;Cowen et al, 1963;Crome et al, 1965;Lyon et al, 1963;Sand bank, 1965], Alzheimer's dementia [Gonatas et al, 1967a], degenerat ing and regenerating axons [Lampert, 1967;BlBmcke et al, 1966], etc., but in our case (5'/2-year-old patient) other types of swellings are found, which do not have any similarity with other swellings.…”

Section: Discussionsupporting

confidence: 59%

Electron Microscopical Study of Neuroaxonal Dystrophy

Coster¹,

Roels²,

Eecken³

1971

Eur Neurol

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A case of a 5½-year-old patient with psycho-motor retardation is presented. It is studied by a cortico-subcortical biopsy of the right frontal lobe, by light and electron microscopy. Paraffin embedded material shows no alterations, but distinct presynaptic and axonal swellings are seen in plastic embedded material. Three morphological types of swelling are described, with increasing dimensions and decreasing number. We have suggested a metabolic disturbance which results in a storage of vesiculo-tubular-structures (which might be malformations of synaptic vesicles), with a chronological evolution of the axonic swelling, going from type 1 to type 3.

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Section: Discussionsupporting

confidence: 59%

Electron Microscopical Study of Neuroaxonal Dystrophy

Coster¹,

Roels²,

Eecken³

1971

Eur Neurol

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“…26 In the neuropil of the cerebral and cerebellar cortex, innumerable tiny vacuoles are observed that may correspond to the pale eosinophilic bodies, which are dystrophic terminal axons in the cerebral cortex of the INAD brain. 20 Immunohistochemistry for ubiquitin reveals positive clefts and vacuoles in the core of the spheroid (Fig. 3).…”

Section: Morphological Characteristics Of Neuroaxonal Dystrophy In Plmentioning

confidence: 98%

“…The spheroids are heavily argyrophilic in some areas and show central rarefaction of argyrophilia in others . Pale eosinophilic bodies that are not impregnated with the standard silver method are also thought to be dystrophic terminal axons . Because of the abundant presence of pale eosinophilic bodies in the cerebral cortex, they were formerly useful for pathological diagnosis by brain biopsy .…”

Section: Neuropathology Of Planmentioning

confidence: 99%

“…20 Because of the abundant presence of pale eosinophilic bodies in the cerebral cortex, they were formerly useful for pathological diagnosis by brain biopsy. 20,21 On electron microscopy, both spheroids and pale eosinophilic bodies comprise tubulovesicular structures that are diagnostic markers for INAD. The presence of Lewy bodies in the brains of patients with INAD has also been reported.…”

Section: Neuropathology Of Planmentioning

confidence: 99%

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Neuroaxonal dystrophy in PLA2G6 knockout mice

et al. 2015

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The PLA2G6 gene encodes group VIA calciumindependent phospholipase A2 (iPLA2β), which belongs to the PLA2 superfamily that hydrolyses the sn-2 ester bond in phospholipids. In the nervous system, iPLA2β is essential for remodeling membrane phospholipids in axons and synapses. Mutated PLA2G6 causes PLA2G6-associated neurodegeneration (PLAN) including infantile neuroaxonal dystrophy (INAD) and adult-onset dystoniaparkinsonism (PARK14), which have unique clinical phenotypes. In the PLA2G6 knockout (KO) mouse, which is an excellent PLAN model, specific membrane degeneration takes place in neurons and their axons, and this is followed by axonal spheroid formation. These pathological findings are similar to those in PLAN. This review details the evidence that membrane degeneration of mitochondria and axon terminals is a precursor to spheroid formation in this disease model. From a young age before the onset, many mitochondria with damaged inner membranes appear in PLA2G6 KO mouse neurons. These injured mitochondria move anterogradely within the axons, increasing in the distal axons. As membrane degeneration progresses, the collapse of the double membrane of mitochondria accompanies axonal injury near impaired mitochondria. At the axon terminals, the membranes of the presynapses expand irregularly from a young age. Over time, the presynaptic membrane ruptures, causing axon terminal degeneration. Although these processes occur in different degenerating membranes, both contain tubulovesicular structures, which are a specific ultrastructural marker of INAD.This indicates that two unique types of membrane degeneration underlie PLAN pathology. We have shown a new pathological mechanism whereby axons degenerate due to defective maintenance and rupture of both the inner mitochondrial and presynaptic membranes. This degeneration mechanism could possibly clarify the pathologies of PLAN, Parkinson disease and neurodegeneration with iron accumulation (NBIA), which are assumed to be due to the primary degeneration of axons.Key words: calcium independent phospholipaseA2β (iPLA2β), infantile neuroaxonal dystrophy (INAD), membrane, mitochondria, PLA2G6.

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“…We have had already a substantial number of studies on the ultrastructural morphology of axonal dystrophy in various morbid conditions of both human (Hedley-Whyte, Gilles & Uzman, 1968;Herman, Huttenlocher & Bensch, 1969;Toga, Bbrard-Badier & Gambarelli-Dubois, 1970;de Coster, Roels & Van der Eecken, 1971;Martin & Martin, 1972;Martin, Trelles & Martin, 1972;Sengel & Stoebner, 1972;Kimura et al, 1974;Liu, Larson & Mizuno, 1974;Vakili, et al, 1977;Scheithauer, et al, 1978;Yagishita, 1979) and animals (Lampert & Pentschew, 1964;Lampert, Blumberg & Penschew, 1964;Blakemore & Cavanagh, 1969;Nakamura & Okamoto, 1973;Johnson, Mehler & Miquel, 1975;Suzuki & Suu, 1978). Its pathogenesis and sequential development as a morbid disturbance of terminal axons, as well as its neurocytological background, however, still remain to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Study of Axonal Dystrophy. Ii. Dystrophy and Atrophy of the Presynaptic Boutons: A Dual Pathology

Fujisawa¹,

Shiraki²

1980

Neuropathology Appl Neurobio

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In succession to the previous quantitative work, a qualitative study has been carried out on the nature of a dual pathology affecting presynaptic boutons in the posterior tract nuclei of ageing rats. Based on the morphology of dystrophic boutons in early stage, it is concluded that the initial and therefore essential characteristic of dystrophic process is an abnormal increase of normal axonal components within the presynaptic boutons, and that various abnormal substructures of spheroids hitherto reported in the literature are probably the results of their secondary metamorphosis. The dystrophic process within the posterior tract nuclei is a selective one, involving presynaptic boutons and preterminal axons only of the posterior tract fibres. Comparison of the frequency of early dystrophic boutons and of fully grown-up spheroids indicates that a small percentage of boutons deriving from posterior tract fibres become dystrophic and of these dystrophic boutons only a small percentage again continue to develop unto large spheroids, throughout lifespan of the animals. On the other hand, in search of a morphological counterpart for the age-related decrease of volume ratio of presynaptic boutons to the neuropil, some dubious atrophic changes were also found in presynaptic boutons, which could have been easily missed from observation if studied qualitatively alone. Accordingly, no less numerous boutons other than dystrophic ones are supposed to atrophy 'independently' and to disappear 'silently' during the same period. The dystrophic and the atrophic changes involve different boutons (of different or the same terminal axons) within the same gray matter. This dual pathology of boutons needs further elucidation of its neurocytopathological as well as neurobiological background in the future.

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Infantile neuroaxonal dystrophy

Cited by 77 publications

References 0 publications

Electron Microscopical Study of Neuroaxonal Dystrophy

Electron Microscopical Study of Neuroaxonal Dystrophy

Neuroaxonal dystrophy in PLA2G6 knockout mice

Study of Axonal Dystrophy. Ii. Dystrophy and Atrophy of the Presynaptic Boutons: A Dual Pathology

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