Demyelinating Leukodystrophy With Total Cortical Cerebellar Atrophy

Thulin, Barbara; McTaggart, David M.; Neubuerger, Karl T.

doi:10.1001/archneur.1968.00470320015001

Cited by 13 publications

(4 citation statements)

References 10 publications

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“…Environmental factors include the possibility that trauma, i.e., a blow to the head (69) or viral infections (70,71), may trigger the onset of symptoms in humans with Krabbe disease, perhaps by induction of proinflammatory mediators. Genetic factors include the presence of modifier genes that interact with the disease, causing gene or influence the disease process and, thus, impact disease progression.…”

Section: Discussionmentioning

confidence: 99%

Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death

Giri

Khan

Rattan

et al. 2006

Journal of Lipid Research

102

122

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Globoid cell leukodystrophy (Krabbe disease) is an inherited neurological disorder caused by the pathogenomic accumulation of psychosine (galactosylsphingosine), a substrate for the deficient enzyme galactocerebroside bgalactosidase. This study underscores the mechanism of action of psychosine in the regulation of oligodendrocyte cell death via the generation of lysophosphatidylcholine (LPC) and arachidonic acid (AA) by the activation of secretory phospholipase A2 (sPLA2). There was a significant increase in the level of LPC, indicating a phospholipase A2 (PLA2)-dependent pathobiology, in the brains of Krabbe disease patients and those of twitcher mice, an animal model of Krabbe disease. In vitro studies of the treatment of primary oligodendrocytes and the oligodendrocyte MO3.13 cell line with psychosine also showed the generation of LPC and the release of AA in a dose-and time-dependent manner, indicating psychosine-induced activation of PLA2. Studies with various pharmacological inhibitors of cytosolic phospholipase A2 and sPLA2 and psychosine-mediated induction of sPLA2 enzymatic activity in media supernatant suggest that psychosine-induced release of AA and generation of LPC is mainly contributed by sPLA2. An inhibitor of sPLA2, 7,7-dimethyl eicosadienoic acid, completely attenuated the psychosine-mediated accumulation of LPC levels, release of AA, and generation of reactive oxygen species, and blocked oligodendroyte cell death, as evident from cell survival, DNA fragmentation, and caspase 3 activity assays. This study documents for the first time that psychosine-induced cell death is mediated via the sPLA2 signaling pathway and that inhibitors of sPLA2 may hold a therapeutic potential for protection against oligodendrocyte cell death and resulting demyelination in Krabbe disease.-Giri, S

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Section: Discussionmentioning

confidence: 99%

Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death

Giri

Khan

Rattan

et al. 2006

Journal of Lipid Research

102

122

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“…Thulin et al (52) which manifested later on and develop mostly a myoclonic duktionsbefunde von vierundzwanzig Kindern auswertet, die an infantilen Spasmen (West-Syndrom) litten. Entsprechend…”

Section: Jeavons and Bowerunclassified

Morphological Aspects of Aetiology and the Course of Infantile Spasms (West-Syndrome)¹

1985

Neuropediatrics

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The present study using the results of the postmortem examination of twenty-four children, who had infantile spasms (West-Syndrome), gives a view of the aetiology and course of the West-Syndrome. According to the time of occurrence of the lesions three groups could be established: one group of six cases with only embryofetal lesions, one group of ten cases with combined embryofetal and peri/postnatal lesions and one group of eight cases with only peri/postnatal lesions. It is significant, that the time of onset of infantile spasms depends on time of manifestation of lesions. In the groups with combined embryofetal and peri/postnatal lesions the seizures were manifested at the same time as in the cases with isolated embryofetal lesions. Even in the group with combined lesions, microdysgenesis was interpreted as being embryofetal. These embryofetal lesions, as opposed to the peri/postnatal lesions thus appear to dominate and thereby to be pathoplastic. From this correlation two thirds of the cases of infantile spasms can be regarded as fetal epilepsies. The question is open if the infantile spasms which are manifested later on and develop mostly a Lennox-Syndrome indeed should be classified as a separate group together with the isolated peri/postnatal lesions.

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“…MS is a disorder of unknown etiology possibly immune mediated in a genetically susceptible individual causing degeneration of already matured myelin. MRI studies in MS including familial cases typically reveal unifocal or multifoci increased signal intensities on T2 weighted image on a background of normal appearing myelin [Lynch et al, 19901. Varieties of hypomyelination and demyelination have been described, although dissimilar to our family [Lowenberg and Hill, 1933;Thulin et al, 1968;Seitelberger, 1970;Baraitser, 1990;Eldridge et al, 19841. The age of onset ranged from 1 112 weeks to 53 years.…”

Section: Discussionmentioning

confidence: 44%

Spinocerebellar degeneration and cerebral hypomyelination in a family

et al. 1995

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The proband is a 24-year-old woman who developed symptoms of a spinocerebellar degeneration in early childhood. Neurological examination revealed normal cognitive function, optic atrophy, dysarthria, titubation, action tremors, increased deep tendon reflexes, Babinski's signs, and a spastic scissoring gait. The magnetic resonance imaging (MRI) showed an abnormal increased signal on long TR images involving white matter throughout the cerebral hemispheres, most striking in the subcortical white matter, and to a lesser degree in the brainstem, compatible with diffuse hypomyelinating or dysmyelinating diseases. Metabolic and chromosomal studies were normal. Her 49-year-old mother developed similar symptoms in her 20s and is now wheelchair-bound. Findings on neurological examination and MRI were similar to her daughter but more severe. The proband's maternal grandfather had a female cousin who had a neurological illness beginning in her 20s with similar symptoms and signs and died at the age of 44 years. Spinocerebellar degenerations are a group of syndromes with similar clinical manifestations but heterogeneous etiology. We report a family with spinocerebellar degeneration with distinct MRI findings compatible with hypomyelination or dysmyelination which has not heretofore been described. This family may represent a new spinocerebellar syndrome due to an abnormality of as yet an undetermined gene.

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Demyelinating Leukodystrophy With Total Cortical Cerebellar Atrophy

Cited by 13 publications

References 10 publications

Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death

Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death

Morphological Aspects of Aetiology and the Course of Infantile Spasms (West-Syndrome)¹

Spinocerebellar degeneration and cerebral hypomyelination in a family

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Demyelinating Leukodystrophy With Total Cortical Cerebellar Atrophy

Cited by 13 publications

References 10 publications

Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death

Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death

Morphological Aspects of Aetiology and the Course of Infantile Spasms (West-Syndrome)1

Spinocerebellar degeneration and cerebral hypomyelination in a family

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Morphological Aspects of Aetiology and the Course of Infantile Spasms (West-Syndrome)¹