Tay-Sachs disease: progression of changes on neuroimaging in four cases

Fukumizu, Michio; Yoshikawa, Hideto; Takashima, Sachio; Sakuragawa, Norio; Kurokawa, Toru

doi:10.1007/bf00598955

Cited by 30 publications

(18 citation statements)

References 3 publications

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“…In the initial phase, high signal intensity on T2-weighted MRI sequences was found at the levels of the basal ganglia and the white matter. The involvement of the white matter had extended during the second phase, and progressive brain atrophy characterized the third phase of the disease [5]. These observations were corroborated by Mugikura et al in another two patients presenting with Tay-Sachs disease [12].…”

Section: Discussionmentioning

confidence: 73%

GM2 gangliosidosis variant B1

Grosso¹,

Farnetani²,

Berardi³

et al. 2003

Journal of Neurology

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Variant B1 is a rare type of GM2 gangliosidosis. Clinically, it shows a wide spectrum of forms ranging from infantile to juvenile. We report the first magnetic resonance imaging (MRI) findings from three patients affected by GM2 gangliosidosis variant B1, two presenting with the infantile form and one with the juvenile form. The MRI appearances of the two patients with the infantile form disease are congruent with those reported for the early-onset type of both Tay-Sachs and Sandhoff diseases, and are characterized by early involvement of the basal ganglia and thalamus with cortical atrophy appearing later. In contrast, the patient with the juvenile form of variant B1 showed progressive cortical and white-matter atrophy of the supratentorial structures and, to a lesser extent, the infratentorial structures. No basal ganglia or thalamic anomalies were observed. Because in the adult forms of both Tay-Sachs and Sandhoff diseases a progressive cerebellar atrophy represents the only abnormality detectable, it appears that an MRI pattern peculiar to GM2 gangliosidosis can be defined. This pattern ranges from the basal ganglia injury associated with the early and severe demyelination process noted in the infantile form of the disease, to cerebellar atrophy with no supratentorial anomalies in the adult form. An "intermediate" MRI picture, with cortical atrophy and mild cerebellar atrophy, but without basal ganglia impairment, can be observed in the juvenile form. In addition, our investigations suggest that MRI abnormalities in GM2 gangliosidosis correlate with the clinical form of the disease rather than with the biochemical variant of the enzymatic defect.

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Section: Discussionmentioning

confidence: 73%

GM2 gangliosidosis variant B1

Grosso¹,

Farnetani²,

Berardi³

et al. 2003

Journal of Neurology

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“…Human and feline GM2 gangliosidosis follow characteristic patterns of neurodegeneration, which on T2 weighted images show increased signal in the white matter and decreased signal in gray matter [66-68]. As glycosphingolipid storage increases in neuronal cell bodies of the gray matter and as the white matter undergoes demyelination [68], these two tissues become indistinguishable on MRI, or isointense.…”

Section: Discussionmentioning

confidence: 99%

“…As glycosphingolipid storage increases in neuronal cell bodies of the gray matter and as the white matter undergoes demyelination [68], these two tissues become indistinguishable on MRI, or isointense. When glycosphingolipid accumulation in gray matter exceeds the lipid composition of white matter, an inversion of intensities is observed [66-68]. AAV gene therapy resulted in significant normalization of intensities in most brain areas regardless of injection route, suggesting that MRI will continue to be a valuable tool in evaluating success of novel therapeutics for GM2 gangliosidosis.…”

Section: Discussionmentioning

confidence: 99%

Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

Bradbury

Gray‐Edwards

Shirley

et al. 2015

Experimental Neurology

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The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated GM2 patients and those in future clinical trials.

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“…The A combination of megalencephaly and leukoencephalopathy with (late) infantile onset is present in several lysosomal disorders, including sphingolipidoses (22)(23)(24)(25)(26)(27) and mucopolysaccharidoses [28,291, and in several disorders of organic acid metabolism, in particular, glutaric aciduria type I {30]. Hemispheric white matter spongiosis may occur in Leigh's syndrome [3 1, 32) and in Kearns-Sayre syndrome [33, 341.…”

Section: Disease Entitymentioning

confidence: 99%

Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children

Knaap

Barth

Stroink

et al. 1995

Annals of Neurology

303

269

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An identical syndrome of cerebral leukoencephalopathy and megalencephaly with infantile onset was discovered in 8 children, including 2 siblings. Neurological findings were initially normal or near normal, despite megalencephaly and magnetic resonance imaging (MRI) evidence of severe white matter affection. Slowly progressive ataxia and spasticity developed, while intellectual functioning was preserved for years after onset of the disorder. MRI characteristics included diffuse abnormality in signal intensity and swelling of the cerebral hemispheral white matter with cyst-like spaces in the frontoparietal and anterior-temporal subcortical areas. MR spectra were relatively mildly abnormal. Screening for inborn errors, especially those that cause either megalencephaly or white matter disease or both was negative. A distinguishing feature of the present disorder is the apparently severe abnormality of the cerebral white matter as demonstrated by MRI, which contrasts with the remarkably slow course of functional deterioration.

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Tay-Sachs disease: progression of changes on neuroimaging in four cases

Cited by 30 publications

References 3 publications

GM2 gangliosidosis variant B1

GM2 gangliosidosis variant B1

Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children

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