A case of infantile Alexander disease diagnosed by magnetic resonance imaging and genetic analysis

Sakakibara, Takafumi; Takahashi, Yukihiro; Fukuda, Kazuyoshi; Inoue, Tomomi; Kurosawa, Tomoko; Nishikubo, Toshiya; Shima, Midori; Taoka, Toshiaki; Aida, Noriko; Tsujino, Seiichi; Kanazawa, Naomi; Yoshioka, Akira

doi:10.1016/j.braindev.2007.02.002

Cited by 8 publications

(3 citation statements)

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“…Inositol and taurine have also been connected to neurodegeneration. Inositol content is of particular interest, because it has been reported to be elevated in several Alexander disease cases (Dinopoulos et al, 2006; Farina et al, 2008; Sakakibara et al, 2007). Increase of inositol concentration is a common finding in models of neurodegeneration (Fisher etal., 2002).…”

Section: Discussionmentioning

confidence: 99%

Alteration of glial‐neuronal metabolic interactions in a mouse model of Alexander disease

Meisingset

Risa

Brenner

et al. 2010

Glia

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Alexander disease is a rare and usually fatal neurological disorder characterized by the abundant presence of protein aggregates in astrocytes. Most cases result from dominant missense de novo mutations in the gene encoding glial fibrillary acidic protein (GFAP), but how these mutations lead to aggregate formation and compromise function is not known. A transgenic mouse line (Tg73.7) over-expressing human GFAP produces astrocytic aggregates indistinguishable from those seen in the human disease, making them a model of this disorder. To investigate possible metabolic changes associated with Alexander disease Tg73.7 mice and controls were injected simultaneously with [1- 13 C]glucose to analyze neuronal metabolism and [1,2-13 C]acetate to monitor astrocytic metabolism. Brain extracts were analyzed by 1 H magnetic resonance spectroscopy (MRS) to quantify amounts of several key metabolites, and by 13 C MRS to analyze amino acid neurotransmitter metabolism. In the cerebral cortex, reduced utilization of [1,2-13 C]acetate was observed for synthesis of glutamine, glutamate, and GABA, and the concentration of the marker for neuronal mitochondrial metabolism, N-acetylaspartate (NAA), was decreased. This indicates impaired astrocytic and neuronal metabolism and decreased transfer of glutamine from astrocytes to neurons compared to control mice. In the cerebellum, glutamine and GABA content and labeling from [1-13 C]glucose were increased. Evidence for brain edema was found in the increased amount of water and of the osmoregulators myo-inositol and taurine. It can be concluded that astrocyte -neuronal interactions were altered differently in distinct regions.

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Section: Discussionmentioning

confidence: 99%

Alteration of glial‐neuronal metabolic interactions in a mouse model of Alexander disease

Meisingset

Risa

Brenner

et al. 2010

Glia

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“…7 Rosenthal fibers accumulating in the brain are thought to contribute to the pathogenesis of Alexander disease and can cause additional complications: for example when accumulating in cerebral spinal fluid pathways may cause obstructive hydrocephalus even in utero. 8 -11 However, Rosenthal fibers are also seen in astrocytic tumors such as astrocytomas. Typically, clinical and radiologic features differentiate Alexander disease from central nervous system malignancies.…”

Section: Discussionmentioning

confidence: 99%

Alexander Disease

Tavasoli

Armangué

et al. 2016

J Child Neurol

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Alexander disease is a leukodystrophy caused by dominant missense mutations in the gene encoding the glial fibrillary acidic protein. Individuals with this disorder often present with a typical neuroradiologic pattern including white matter abnormalities with brainstem involvement, selective contrast enhancement, and structural changes to the basal ganglia/thalamus. In rare cases, focal lesions have been seen and cause concern for primary malignancies. Here the authors present an infant initially diagnosed with a chiasmatic astrocytoma that was later identified as having glial fibrillary acidic protein mutation-confirmed Alexander disease. Pathologic and radiologic considerations that were helpful in arriving at the correct diagnosis are discussed.

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“…High signal intensity on T2-weighted images are reported to correspond to deposits of Rosenthal fibers or associated demyelination, and because these fibers cause breakdown of the blood–brain barrier, contrast enhancement is seen in sites with significant deposits [ 3 , 4 ]. Loss of brain tissue also leads to cyst formation.…”

Section: Discussionmentioning

confidence: 99%

Infantile-onset Alexander disease in a child with long-term follow-up by serial magnetic resonance imaging: a case report

et al. 2013

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IntroductionAlexander disease is a rare disorder resulting from a glial fibrillary acidic protein gene mutation which causes progressive degeneration of white matter. With the usual poor prognosis, there are few case reports with long-term follow-up. We report the five-year clinical course of Alexander disease in one case using serial magnetic resonance imaging.Case presentationA 12-month-old Japanese male was referred to the pediatrics department in our hospital because of developmental retardation. Alexander disease was diagnosed by gene examination of the mutation of a glial fibrillary acidic protein. Magnetic resonance imaging findings showed abnormalities in white matter, deep gray matter, and medulla oblongata. Serial magnetic resonance imaging examinations until the age of five were performed and changes in magnetic resonance imaging findings were compared to the progression in clinical symptoms.ConclusionAlexander disease is a very rare disease with a variety of clinical phenotypes. Therefore serial magnetic resonance imaging studies for long-term survival infantile cases including our case may be important in the analysis of the pathophysiological mechanism.

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A case of infantile Alexander disease diagnosed by magnetic resonance imaging and genetic analysis

Cited by 8 publications

References 8 publications

Alteration of glial‐neuronal metabolic interactions in a mouse model of Alexander disease

Alteration of glial‐neuronal metabolic interactions in a mouse model of Alexander disease

Alexander Disease

Infantile-onset Alexander disease in a child with long-term follow-up by serial magnetic resonance imaging: a case report

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