Proton MR Spectroscopic Imaging in Pelizaeus-Merzbacher Disease

Pizzini, Francesca; Fatemi, Ali; Barker, Peter B.; Moser, Hugo W.; Naidu, Sakkubai; Beltramello, Alberto

doi:10.1177/197140090301600320

Cited by 18 publications

(33 citation statements)

References 24 publications

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“…PelizaeusMerzbacher disease has also been associated with alterations in NAA and NAAG levels in brain or cerebrospinal fluid. Increased levels of NAA in white matter have been reported by some researchers (Hanefeld et al, 2005;Takanashi et al, 2002), whereas other studies have reported decreased levels of NAA in white matter in this dysmyelinating disease (Pizzini et al, 2003). Increased NAAG in the cerebrospinal fluid has also been reported in patients with Pelizaeus-Merzbacher disease (Burlina et al, 2006a).…”

Section: Other Genetic Disruptions In Myelinogenesismentioning

confidence: 79%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,213

1,126

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The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal CNS development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.

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Section: Other Genetic Disruptions In Myelinogenesismentioning

confidence: 79%

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Moffett

Ross

Arun

et al. 2007

Progress in Neurobiology

1,213

1,126

View full text Add to dashboard Cite

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“…In some patients there is a tigroid or patchy T2-hyperintensity that involves the supratentorial white matter as well as the cerebellum and brainstem. This pattern is more common in those with SPG II, whereas the confluent white matter is more common in the severe connatal form 26 . Loss of white matter volume and atrophy occur with time.…”

Section: Pelizaeus-merzbacher Disease (Pmd)mentioning

confidence: 88%

“…Loss of white matter volume and atrophy occur with time. Pathologically this correlates with axonal loss, for which MRS has been useful by showing a decrease in levels of NAA due to neuronal axonal degeneration, whereas on spectroscopy elevated levels of choline and creatine appear to arise from the increased astrocytic processes 26 .…”

Section: Pelizaeus-merzbacher Disease (Pmd)mentioning

confidence: 98%

Inherited White Matter Diseases

Zimmerman

2006

Rivista di Neuroradiologia

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“…By contrast, decrease in Cho or increase in Cr can be detected in hypomyelination [54]. In dysmyelinating diseases such as the Pelizaeus-Merzbacher disease, both increases and decreases in Cho have been described [12,55].…”

Section: Demyelinating and Dysmyelinating Diseasesmentioning

confidence: 99%

Proton Magnetic Resonance Spectroscopy in Brain Metabolic Disorders

Stefano

Mortilla

2007

Clin Neuroradiol

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Metabolic disorders of the central nervous system (CNS) include pathologies with extremely different pathogenesis. The clinical diagnosis of these disorders is often very difficult and requires sophisticated laboratory investigations. Proton magnetic resonance (MR) spectroscopy ( 1 H-MRS) has recently been used in a number of clinical studies to supplement conventional MRI as it is able to provide in vivo biochemical assay of a given brain tissue. Brain data on several neurometabolic diseases suggest that 1 H-MRS can provide in vivo chemical-pathologic characterization of the abnormality visualized by magnetic resonance imaging (MRI) and can detect metabolic alterations in tissue appearing normal on conventional MRI. This may help for differential diagnosis and can be important in the evaluation of disease outcome. Indices provided by 1 H-MRS have been demonstrated to be relevant to patients' clinical status, to represent sensitive indicators of early neurologic involvement and to be helpful in monitoring effects of therapeutic interventions. This suggests that, in the next future, a more extensive use of brain 1 H-MRS in the management of patients with metabolic disorders affecting CNS should be encouraged. ZusammenfassungStoffwechselstörungen des zentralen Nervensystems (ZNS) umfassen Erkrankungen mit äußerst unterschiedlicher Pathogenese. Klinisch gestaltet sich die Diagnose dieser Erkrankungen häufig ausgesprochen schwierig und erfordert daher differenzierte Labortests. Da die Protonen-Magnetresonanzspektroskopie ( 1 H-MRS) ein biochemisches Profil des untersuchten Hirngewebes in vivo erstellt, wird sie in letzter Zeit in einer Reihe klinischer Studien eingesetzt, um die konventionelle Magnetresonanztomographie (MRT) zu ergänzen. Die daraus für verschiedene Stoffwechselerkrankungen des Gehirns gewonnenen Daten legen nahe, dass 1 H-MRS sowohl die chemisch-pathologischen In-vivo-Charakteristika der mittels MRT visualisierten Auffälligkeiten als auch Stoffwechselveränderungen innerhalb des übrigen, in der MRT normal erscheinenden Gewebes zu erfassen vermag. Das kann differentialdiagnostisch und prognostisch von Nutzen sein. So wurde bereits gezeigt, dass spektroskopische Indizes den klinischen Zustand von Patienten reflektieren, dass sie sensitive Indikatoren für eine frühe neurologische Beteiligung bei Stoffwechselerkrankungen darstellen und dass sie hilfreich sein können, um Therapieeffekte zu überwachen. Das legt nahe, dass die 1 H-MRS in Zukunft verstärkt bei das ZNS erfassenden Stoffwechselstörungen angewendet werden sollte.

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Proton MR Spectroscopic Imaging in Pelizaeus-Merzbacher Disease

Cited by 18 publications

References 24 publications

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

Inherited White Matter Diseases

Proton Magnetic Resonance Spectroscopy in Brain Metabolic Disorders

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