Decreased T2 signal in the thalami may be a sign of lysosomal storage disease

Autti, Taina; Joensuu, Raimo; Åberg, L.

doi:10.1007/s00234-007-0220-6

Cited by 78 publications

(56 citation statements)

References 98 publications

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“…It is likely that targeting the thalamus directly could further increase efficacy because it is a site of significant disease and it is the first region of the brain to be affected in CLN1 disease (14). Indeed, the thalamus consistently appears to be an important and early disease focus in many different LSDs, as is revealed by T2 imaging of these patients (43), and pronounced thalamic pathology has been shown in mouse models of all forms of NCL (reviewed in ref. 44) and all other LSDs we have examined (e.g., 45,46).…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of treating the spinal cord and brain in CLN1 disease

Shyng

Nelvagal

Dearborn

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

101

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Infantile neuronal ceroid lipofuscinosis (INCL, or CLN1 disease) is an inherited neurodegenerative storage disorder caused by a deficiency of the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1). It was widely believed that the pathology associated with INCL was limited to the brain, but we have now found unexpectedly profound pathology in the human INCL spinal cord. Similar pathological changes also occur at every level of the spinal cord of PPT1-deficient (Ppt1 −/− ) mice before the onset of neuropathology in the brain. Various forebrain-directed gene therapy approaches have only had limited success in Ppt1 −/− mice. Targeting the spinal cord via intrathecal administration of an adeno-associated virus (AAV) gene transfer vector significantly prevented pathology and produced significant improvements in life span and motor function in Ppt1 −/− mice. Surprisingly, forebrain-directed gene therapy resulted in essentially no PPT1 activity in the spinal cord, and vice versa. This leads to a reciprocal pattern of histological correction in the respective tissues when comparing intracranial with intrathecal injections. However, the characteristic pathological features of INCL were almost completely absent in both the brain and spinal cord when intracranial and intrathecal injections of the same AAV vector were combined. Targeting both the brain and spinal cord also produced dramatic and synergistic improvements in motor function with an unprecedented increase in life span. These data show that spinal cord pathology significantly contributes to the clinical progression of INCL and can be effectively targeted therapeutically. This has important implications for the delivery of therapies in INCL, and potentially in other similar disorders.infantile Batten disease | adeno-associated virus | spinal cord | brain | combination therapy

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Section: Discussionmentioning

confidence: 99%

Synergistic effects of treating the spinal cord and brain in CLN1 disease

Shyng

Nelvagal

Dearborn

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

101

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“…We have not seen this finding reported in any earlier studies. A review of the literature 23 on lysosomal storage diseases attributes thalamic T2 hypointensity to an accumulation of paramagnetic substances such as iron, free radicals, and deoxygenated hemoglobin. This explanation is controversial, however; the phenomenon is more likely related to changes in tissue viscosity due to an accumulation of macromolecules and lipids.…”

Section: Mr Spectroscopymentioning

confidence: 99%

Toward a Better Understanding of Brain Lesions during Metachromatic Leukodystrophy Evolution

Martin¹,

Sevin²,

Lazarus

et al. 2012

AJNR Am J Neuroradiol

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“…This case illustrates that lysosomal storage disorders should be considered. Hypointensities in the basal ganglia and the thalamus have been described in other lysosomal storage diseases, such as fucosidosis and mucoliposidosis, but were not classified as NBIA (Autti et al 2007). The pathogenetic mechanisms underlining the basal ganglia abnormalities in AMD remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Comparable mechanisms could play a role in AMD. Alternatively, the hypointensities could be caused by alterations in tissue viscosity by accumulation of lysosomal storage material and give similar resonances on MRI as that of iron (Autti et al 2007). However, one would expect the abnormalities to be present in almost all lysosomal storage disorders, instead of in a selected number of disorders (Autti et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Neurodegeneration with Brain Iron Accumulation on MRI: An Adult Case of α-Mannosidosis

et al. 2011

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Case: A 34-year-old woman was referred to our hospital with progressive movement disorders and neurodegeneration with brain iron accumulation and enlargement of the frontal diploe on the MRI. Metabolic testing revealed that she had a-mannosidosis (AMD), a lysosomal storage disorder.Background: AMD is a rare genetic disorder that causes a-mannosidase deficiency resulting in lysosomal accumulation of undigested oligosaccharides. The symptoms of AMD consist of facial and skeletal deformities combined with progressive psychiatric and neurological complaints, especially ataxia and mental retardation. Bilateral patellar dislocation and hearing impairment are frequent.Discussion: The movement disorders we found in our patient have not been reported previously, but they are likely late symptoms of this progressive disorder. The iron deposits in the basal ganglia have also not been reported in AMD and are yet of unknown significance. Lysosomal storage disorders, such as AMD, should be considered in patients with progressive neurologic conditions and neurodegeneration with brain iron accumulation on MRI.

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Decreased T2 signal in the thalami may be a sign of lysosomal storage disease

Abstract: A decrease in T2 signal intensity in the thalami seems to be a sign of lysosomal disease.

Cited by 78 publications

References 98 publications

Synergistic effects of treating the spinal cord and brain in CLN1 disease

Synergistic effects of treating the spinal cord and brain in CLN1 disease

Toward a Better Understanding of Brain Lesions during Metachromatic Leukodystrophy Evolution

Neurodegeneration with Brain Iron Accumulation on MRI: An Adult Case of α-Mannosidosis

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