Natural History of Canavan Disease Revealed by Proton Magnetic Resonance Spectroscopy (1H‐MRS) and Diffusion-weighted MRI
Abstract
Canavan disease is a childhood leukodystrophy caused by mutations in the gene for human aspartoacylase ( ASPA), which leads to an abnormal accumulation of the substrate molecule N-acetyl-aspartate (NAA) in the brain. This study was designed to model the natural history of Canavan disease using MRI and proton magnetic resonance spectroscopy ( (1)H-MRS). NAA and various indices of brain structure (morphology, quantitative T1, fractional anisotropy, apparent diffusion coefficient) were measured in white and gray matter regions during the progression of Canavan disease. A mixed-effects statistical model was used to fit all outcome measures. Longitudinal data from 28 Canavan patients were directly compared in each brain region with reference data obtained from normal, age-matched pediatric subjects. The resultant model can be used to non-invasively monitor the natural history of Canavan disease or related leukodystrophies in future studies involving drug, gene therapy, or stem cell treatments.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In humans, Canavan disease manifests in early postnatal life, with diagnosis typically occurring after key neurodevelopmental milestones have been missed.
“In humans, Canavan disease manifests in early postnatal life, with diagnosis typically occurring after key neurodevelopmental milestones have been missed”
From Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease (2021) · cites this paper as [7]
SCWM in Canavan patients presents with severe abnormalities, such as a swollen aspect, and progressive fractional anisotropic abnormalities, as documented by diffusion tensor imaging (DTI).
“SCWM in Canavan patients presents with severe abnormalities, such as a swollen aspect, and progressive fractional anisotropic abnormalities, as documented by diffusion tensor imaging (DTI).”
From Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease (2021) · cites this paper as [7]
Cited by
Sorted by citations
Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality
Hudry, E., & Vandenberghe, L. H. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.017 · Cited by 368 · see citing works
Long-term follow-up after gene therapy for canavan disease
Leone, P., Shera, D., McPhee, S. W. J., Francis, J. S., Kolodny, E. H., Bilaniuk, L. T., Wang, D.-J., Assadi, M., Goldfarb, O., Goldman, H. W., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003454 · Cited by 307 · see citing works
“The reference ranges provided for each region (yellow shading) are 95% confidence intervals (CIs) based on four reference subjects without Canavan disease aged 16 to 36 months (10).”
BackgroundMethodInfluentialSelf-citationIn vivo magnetic resonance spectroscopy: basic methodology and clinical applications
van der Graaf, M. (2009) · European Biophysics Journal · doi:10.1007/s00249-009-0517-y · Cited by 274 · see citing works
“Because of a deficiency in the enzyme aspartoacylase, NAA accumulates in the mitochondria and impairs myelin synthesis resulting in this severe whitematter disease (Janson et al. 2006).”
BackgroundEvidence for neuroinflammation and neuroprotection in HCV infection-associated encephalopathy
Bokemeyer, M., Ding, X.-Q., Goldbecker, A., Raab, P., Heeren, M., Arvanitis, D., Tillmann, H. L., Lanfermann, H., & Weißenborn, K. (2010) · Gut · doi:10.1136/gut.2010.217976 · Cited by 110 · see citing works
Differential diagnosis of cerebellar atrophy in childhood
Poretti, A., Wolf, N. I., & Boltshauser, E. (2007) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2007.07.010 · Cited by 99 · see citing works
Metabolic Aspects of Neuron-Oligodendrocyte-Astrocyte Interactions
Amaral, A. I., Meisingset, T. W., Kotter, M., & Sonnewald, U. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00054 · Cited by 89 · see citing works
Localisation of N-acetylaspartate in oligodendrocytes/myelin
Nordengen, K., Heuser-Loy, C., Rinholm, J. E., Matalon, R. K., & Gundersen, V. (2013) · Brain Structure and Function · doi:10.1007/s00429-013-0691-7 · Cited by 75 · see citing works
“It is known that there is a large build-up of NAA in Canavan disease (Matalon et al. 2000; Janson et al. 2006; Traka et al. 2008; Mersmann et al. 2011).”
BackgroundClinical Applications Involving CNS Gene Transfer
Kantor, B., McCown, T., Leone, P., & Gray, S. J. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00002-0 · Cited by 74 · see citing works
Self-citationÇakmakçı, H., Pekçevik, Y., Yiş, U., Ünalp, A., & Kurul, S. H. (2009) · European Journal of Radiology · doi:10.1016/j.ejrad.2009.05.048 · Cited by 60 · see citing works
Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan disease
Assadi, M., Janson, C. G., Wang, D.-J., Goldfarb, O., Suri, N., Bilaniuk, L. T., & Leone, P. (2010) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2009.11.006 · Cited by 58 · see citing works
Self-citationMetabolomics of Cerebrospinal Fluid from Humans Treated for Rabies
O’Sullivan, A. M., Willoughby, R. E., Mishchuk, D. O., Alcarraz, B., Cabezas, C., Condori, R. E., David, D., Encarnacion, R., Fatteh, N., Fernández, J., et al. (2012) · Journal of Proteome Research · doi:10.1021/pr3009176 · Cited by 55 · see citing works
Baslow, M. H., & Guilfoyle, D. N. (2012) · Biochimie · doi:10.1016/j.biochi.2012.10.023 · Cited by 51 · see citing works
Francis, J. S., Wojtas, I., Markov, V., Gray, S. J., McCown, T. J., Samulski, R. J., Bilaniuk, L. T., Wang, D.-J., De Vivo, D. C., Janson, C. G., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.10.001 · Cited by 49 · see citing works
“Previously, we had described two sisters with an unusually mild presentation of Canavan disease, due to compound heterozygosity with R71H mutation(Janson et al., 2006a).”
BackgroundSelf-citationAbsence of age-related prefrontal NAA change in adults with autism spectrum disorders
Aoki, Y. Y., Abe, O., Yahata, N., Kuwabara, H., Natsubori, T., Iwashiro, N., Takano, Y., Inoue, H., Kawakubo, Y., Gonoi, W., et al. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.108 · Cited by 43 · see citing works
Francis, J. S., Markov, V., Wojtas, I. D., Gray, S., McCown, T., Samulski, R. J., Figueroa, M., & Leone, P. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.01.009 · Cited by 41 · see citing works
“In addition, SCWM in Canavan patients presents with severe abnormalities, such as a swollen aspect, and progressive fractional anisotropic abnormalities, as documented by diffusion tensor imaging (DTI).(7) Given that white matter has a significant capacity for remyelination, even in the adult brain, the persistence of…”
BackgroundSelf-citationBilateral symmetrical basal ganglia and thalamic lesions in children: an update (2015)
Zuccoli, G., Yannes, M. P., Nardone, R., Bailey, A. L., & Goldstein, A. C. (2015) · Neuroradiology · doi:10.1007/s00234-015-1568-7 · Cited by 40 · see citing works
“An NAA peak represents the hallmark MRS feature of Canavan disease [84].”
BackgroundMyelin Lipid Abnormalities in the Aspartoacylase-Deficient Tremor Rat
Wang, J., Leone, P., Wu, G., Francis, J. S., Hong Li, A., Jain, M. R., Serikawa, T., & Ledeen, R. W. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9726-5 · Cited by 39 · see citing works
“This autosomal recessive childhood disorder is characterized by CNS swelling and spongy degeneration of white matter, along with accumulation of N-acetylaspartate (NAA) in brain and urine [3, 4].”
BackgroundSelf-citationMadhavarao, C. N., Arun, P., Anikster, Y., Mog, S. R., Staretz‐Chacham, O., Moffett, J. R., Grunberg, N. E., Gahl, W. A., & Namboodiri, A. M. A. (2009) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-009-1155-3 · Cited by 38 · see citing works
“In a study on ASPAD patients (Janson et al. 2006), increase in whole-brain NAA during 12–24 month in most brain regions was reported compared with 1 For weights outside the standard ranges, human equivalent dose is calculated using the formula: HED = animal dose in mg/kg (animal weight in kg/human…”
BackgroundMethodInfluentialAoki, Y. Y., Aoki, A., & Suwa, H. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.78 · Cited by 37 · see citing works
“For example, ‘NAA trapping theory’ suggests that NAA may increase even in cases of dysfunctional metabolism of the astrocytes or oligodendrocytes.(58) For example, patients with Canavan’s disease, caused by mutations in the gene that codes for the enzyme of aspartoacylase, which is necessary for NAA metabolism, have r…”
BackgroundImaging Manifestations of the Leukodystrophies, Inherited Disorders of White Matter
Yang, E., & Prabhu, S. P. (2014) · Radiologic Clinics of North America · doi:10.1016/j.rcl.2013.11.008 · Cited by 35 · see citing works
Magnetic Resonance Spectroscopy in Metabolic Disorders
Rossi, A., & Biancheri, R. (2013) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2012.12.013 · Cited by 32 · see citing works
Lactate peak on brain MRS in children with syndromic mitochondrial diseases
Chi, C., Lee, H.-F., Tsai, C., et al. (2011) · Journal of the Chinese Medical Association · doi:10.1016/j.jcma.2011.05.006 · Cited by 31 · see citing works
The pathogenesis of, and pharmacological treatment for, Canavan disease
Wei, H., Moffett, J. R., Amanat, M., Fatemi, A. S., Tsukamoto, T., Namboodiri, A. M. A., & Slusher, B. S. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.05.019 · Cited by 30 · see citing works
Baslow, M. H., & Guilfoyle, D. N. (2009) · Neurochemical Research · doi:10.1007/s11064-009-9958-z · Cited by 30 · see citing works
“Metabolic hallmarks of the disease include a 20‐30% elevation in the total of neuron-specific N-acetylaspartate (NAA) and its anabolic product N-acetylaspartylglutamate (NAAG) in brain gray matter (GM) and white matter (WM) [ 2 ].”
BackgroundLeukodystrophies and other genetic metabolic leukoencephalopathies in children and adults
Kohlschütter, A., Bley, A. E., Brockmann, K., Gärtner, J., Krägeloh‐Mann, I., Rolfs, A., & Schöls, L. J. (2009) · Brain and Development · doi:10.1016/j.braindev.2009.03.014 · Cited by 29 · see citing works
Pathophysiology and Treatment of Canavan Disease
Pleasure, D., Guo, F., Chechneva, O. V., Bannerman, P. G. C., McDonough, J. A., Burns, T., Wang, Y., & Hull, V. L. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2693-6 · Cited by 27 · see citing works
“In vivo proton nuclear magnetic resonance spectroscopy (1H-MRS) documents a 30% or greater elevation in brain NAA concentration ([NAAB]) [10].”
BackgroundBaslow, M. H. (2009) · Amino Acids · doi:10.1007/s00726-009-0232-0 · Cited by 24 · see citing works
Sohn, J., Bannerman, P. G. C., Guo, F., Burns, T., Miers, L. A., Croteau, C., Singhal, N. K., McDonough, J. A., & Pleasure, D. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.2013-16.2016 · Cited by 23 · see citing works
Quantitative MRI in leukodystrophies
Stellingwerff, M. D., Pouwels, P. J. W., Roosendaal, S. D., Barkhof, F., & van der Knaap, M. S. (2023) · NeuroImage Clinical · doi:10.1016/j.nicl.2023.103427 · Cited by 22 · see citing works
“DTI-measures are sensitive biomarkers and have previously shown their value in various other leuko-dystrophies, such as Canavan disease (Janson et al., 2006; Kimiskidis et al., 2017), Adult-onset autosomal Dominant Leukodystrophy (Zanigni et al., 2015), hypomyelinating PLP1-related disorders…”
Pederzolli, C. D., Rockenbach, F. J., Zanin, F. R., et al. (2009) · Metabolic Brain Disease · doi:10.1007/s11011-009-9137-6 · Cited by 22 · see citing works
“Brain atrophy progressively increases over time in CD patients, and whole-brain NAA rises linearly and continuously (Janson et al. 2006).”
BackgroundAlternating hemiplegia of childhood: evolution over time and mouse model corroboration
Uchitel, J., Wallace, K., Tran, L., et al. (2021) · Brain Communications · doi:10.1093/braincomms/fcab128 · Cited by 21 · see citing works
In Vivo NMR Studies of the Brain with Hereditary or Acquired Metabolic Disorders
Sherry, E. B., Lee, P., & Choi, I.-Y. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1772-1 · Cited by 18 · see citing works
Merrill, S. T., Nelson, G. R., Longo, N., et al. (2016) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-016-0549-1 · Cited by 20 · see citing works
Non-genetic therapeutic approaches to Canavan disease
Roscoe, R. B., Elliott, C., Ζάρρος, Α., et al. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.05.012 · Cited by 19 · see citing works
Neuroprotective role of lipoic acid against acute toxicity of N-acetylaspartic acid
Pederzolli, C. D., Rosa, A. P., de Oliveira, A. S., et al. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-010-0547-x · Cited by 18 · see citing works
“The neuropathological findings of the disease include an extensive loss of myelin with edema and vacuolation in the white matter of the brain [17, 18], the presence of swollen astrocytes, as well as distorted and elongated mitochondria [19], and progressive brain atrophy [14, 20].”
BackgroundFeng, L., Chao, J., Zhang, M., Pacquing, E., Hu, W., & Shi, Y. (2023) · iScience · doi:10.1016/j.isci.2023.108037 · Cited by 17 · see citing works
Leone, P., Lober, R. M., Francis, J. S., Flamini, O., Cecil, K. M., Shera, D. M., & Janson, C. G. (2025) · Nature Medicine · doi:10.1038/s41591-025-03919-w · Cited by 12 · see citing works
Self-citationClinical 1H MRS in childhood neurometabolic diseases — part 2: MRS signatures
Whitehead, M. T., Lai, L. M., & Blüml, S. (2022) · Neuroradiology · doi:10.1007/s00234-022-02918-9 · Cited by 12 · see citing works
“Although NAA may elevated in the first year of life, on average, NAA begins to increase diffusely in the brain between 12 and 24 months in Canavan disease and has a rostral-caudal gradient and periventricular predominance irrespective of the genetic defect [2, 3, 6, 11].”
BackgroundBrain neurochemical and hemodynamic findings in the NY1DD mouse model of mild sickle cell disease
Cui, M., Suzuka, S. M., Branch, N. A., Ambadipudi, K., Thangaswamy, S., Acharya, S. A., Billett, H. H., & Branch, C. A. (2017) · NMR in Biomedicine · doi:10.1002/nbm.3692 · Cited by 11 · see citing works
An Atypical Case of Canavan Disease With Stroke-Like Presentation
Delaney, K. E., Kralik, S. F., Hainline, B. E., et al. (2014) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2014.10.019 · Cited by 10 · see citing works
Novel proton MR spectroscopy findings in adenylosuccinate lyase deficiency
Zulfiqar, M., Lin, D. D. M., van der Graaf, M., et al. (2012) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.23852 · Cited by 10 · see citing works
Pederzolli, C. D., Mescka, C. P., Magnusson, A. S., et al. (2010) · Metabolic Brain Disease · doi:10.1007/s11011-010-9202-1 · Cited by 9 · see citing works
“Brain atrophy progressively increases over time in CD patients and this occurs in parallel with NAA rise (Janson et al. 2006).”
BackgroundInherited or acquired metabolic disorders
Eichler, F., Ratai, E., Carroll, J. J., & Masdeu, J. C. (2016) · Handbook of clinical neurology · doi:10.1016/b978-0-444-53485-9.00029-5 · Cited by 9 · see citing works
1H-MR spectroscopy of adult-onset autosomal dominant leukodystrophy with autonomic symptoms
Finnsson, J., Melberg, A., & Raininko, R. (2013) · Neuroradiology · doi:10.1007/s00234-013-1174-5 · Cited by 8 · see citing works
Ahmed, S. S., & Gao, G. (2014) · JIMD Reports · doi:10.1007/8904_2014_356 · Cited by 7 · see citing works
“A second clinical trial (Janson et al. 2006) involved intracranial injections of rAAV2 vectors into the parietal, occipital, and frontal lobes in the brain of a large group of CD patients [FDA-IND#9119; NIH (RAC) #0001-381].”
BackgroundDaci, R., Gray‐Edwards, H. L., Shazeeb, M. S., Vardar, Z., Vachha, B. A., Cataltepe, O. I., & Flotte, T. R. (2024) · Human Gene Therapy · doi:10.1089/hum.2024.057 · Cited by 7 · see citing works
Advanced Neuroimaging Techniques: Basic Principles and Clinical Applications
Griauzde, J. M., & Srinivasan, A. (2017) · Journal of Neuro-Ophthalmology · doi:10.1097/wno.0000000000000539 · Cited by 6 · see citing works
Rossler, L., Lemburg, S. P., Weitkämper, A., et al. (2022) · Journal of Ultrasound · doi:10.1007/s40477-022-00667-2 · Cited by 6 · see citing works
Rahimian, E., D’Arco, F., Sudhakar, S. V., et al. (2024) · Neuroradiology · doi:10.1007/s00234-024-03388-x · Cited by 5 · see citing works
“MRI studies also show diffuse leu - kodystrophy and diffusion restriction in a significant portion of the cases [1, 6, 7].”
Magnetic Resonance Spectroscopy (MRS) of the Brain
Fayed, N., & Gonzalez-Toledo, E. (2014) · Elsevier eBooks · doi:10.1016/b978-0-444-53632-7.00318-x · Cited by 5 · see citing works
Advances in MR Imaging of Leukodystrophies
Ratai, E., Caruso, P. A., & Eichler, F. (2012) · InTech eBooks · doi:10.5772/25151 · Cited by 5 · see citing works
“Their MRI shows diffuse involvement of white matter including the subcortical U fibers (15).”
BackgroundPatel, S. H., Panagiotakaki, E., Papadopoulou, M. T., Fons, C., Grandis, E. D., Vezyroglou, A., Balestrini, S., Hong, H., Liu, B., Prange, L., et al. (2023) · Journal of Child Neurology · doi:10.1177/08830738231197861 · Cited by 5 · see citing works
Neuroimaging in Children With Inherited Metabolic Epilepsies
Latzer, I. T., Yang, E., de Figueiredo, V. L. P., Huang, S. Y., Matsubara, T., & Pearl, P. L. (2025) · Neurology · doi:10.1212/wnl.0000000000213485 · Cited by 4 · see citing works
Canavan Disease: A Novel Mutation
Schober, H., Luetschg, J., Höliner, I., Kalb, S., & Simma, B. (2011) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2011.06.011 · Cited by 4 · see citing works
Patel, S. H., Panagiotakaki, E., Liu, B., Fons, C., Prange, L., Papadopoulou, M. T., Boggs, A., Grandis, E. D., Vezyroglou, A., Fortunato, F., et al. (2025) · Annals of the Child Neurology Society · doi:10.1002/cns3.70037 · Cited by 3 · see citing works
Urine N -Acetylaspartate Distinguishes Phenotypes in Canavan Disease
Nagy, A. M., Eichler, F., Bley, A. E., et al. (2024) · Human Gene Therapy · doi:10.1089/hum.2024.168 · Cited by 3 · see citing works
“24,39 A recent study put forth that the atrophy could be driven by a mechanism in which neuronal cells are unable to differentiate and mature in the CD CNS environment.”
Jurdáková, H., Górová, R., Addová, G., et al. (2019) · Monatshefte für Chemie - Chemical Monthly · doi:10.1007/s00706-018-2349-x · Cited by 3 · see citing works
Glicksman, S., Borgen, C., Blackstein, M., Gordon, A., Hanon, I., Kusin, D., Leibowitz, B., & Halle, J. (2012) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.2012.01576.x · Cited by 3 · see citing works
Canavan Disease: A Neurometabolic Disease Caused By Aspartoacylase Deficiency
Lienhard, U., & Sass, J. O. (2011) · DergiPark (Istanbul University) · doi:10.17334/jps.44686 · Cited by 3 · see citing works
Ocular Manifestations of Inborn Errors of Metabolism
Ganesh, A., Al-Murshedi, F., Al-Zuhaibi, S. S., & Al‐Thihli, K. (2017) · Springer eBooks · doi:10.1007/978-3-319-18389-3_13 · Cited by 5 · see citing works
Canavan Disease and Recent Advances
Dirik, M. A., Şanlıdağ, B., Dırık, E., & Bulakbaşı, N. (2021) · Cyprus Journal of Medical Sciences · doi:10.5152/cjms.2021.953 · Cited by 2 · see citing works
Advanced imaging in paediatric neuroradiology
Koçak, M. (2009) · Pediatric Radiology · doi:10.1007/s00247-009-1230-9 · Cited by 2 · see citing works
“To mention a few, elevated NAA is observed in Canavan disease [94].”
BackgroundBaslow, M. H., & Guilfoyle, D. N. (2014) · Journal of Genetic Disorders & Genetic Reports · doi:10.4172/2327-5790.1000110 · Cited by 2 · see citing works
Jurdáková, H., Górová, R., Addová, G., Behúlová, D., & Ostrovský, I. (2016) · Chemical Papers · doi:10.1007/s11696-016-0033-3 · Cited by 2 · see citing works
“1991) and magnetic resonance imaging (MRI) (Nowell et al. 1988; Brismar et al. 1990; Marks et al. 1991; Toft et al. 1993; Engelbrecht et al. 1995; Janson et al. 2006), can also show the pathological changes of the white matter in the brain.”
InfluentialNeissi, M., Sheikh‐Hosseini, M., & Asl, J. M. (2021) · International Journal of Biomedicine · doi:10.21103/article11(4)_cr2 · Cited by 1 · see citing works
Functional Neuroimaging in Clinical Neurology: A Comprehensive Review of Commonly Used Modalities
Salardini, A. (2025) · Seminars in Neurology · doi:10.1055/a-2773-5481 · Cited by 1 · see citing works
Viral Vector Gene Delivery to the Brain for Treating Neurogenetic Diseases
Ramos, L., Hunter, J. E., & Wolfe, J. H. N. (2017) · Springer eBooks · doi:10.1007/978-3-319-57696-1_4 · Cited by 2 · see citing works
Nuclear Magnetic Resonance of Cerebrospinal Fluid: The Neurometabolome
Mochel, F. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9780511996634.016 · Cited by 1 · see citing works
Proton Magnetic Resonance Spectroscopy: Applications in Neonatal Medicine
Ashwal, S., Bartnik‐Olson, B., & Holshouser, B. A. (2012) · Springer eBooks · doi:10.1007/978-1-4419-5864-8_8 · Cited by 1 · see citing works
Elliott, C., Al‐Humadi, H., Gutierrez‐Quintana, R., et al. (2018) · Annals of Research Hospitals · doi:10.21037/arh.2018.04.01 · Cited by 1 · see citing works
“In what appears to be a major study in the field, von Jonquieres et al. (3) have recently shown that although increased CNS NAA levels predict pathological severity in CD mice, these same high levels are not neurotoxic per se.”
BackgroundInfluentialNosrati, R., Balasubramanian, M., & Mulkern, R. V. (2021) · Magnetic Resonance in Medicine · doi:10.1002/mrm.28644 · Cited by 1 · see citing works
Magnetic resonance spectroscopy in pediatric white matter disease
Brockmann, K., Dechent, P., & Hanefeld, F. A. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9781139193481.055
Rossi, A., & Hoffmann, C. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9781139030854.025
The Effects of Hypothyroidism Due to Iodine Deficiency in Neonatal Brain
Akıncı, A., & Karakaş, H. M. (2009) · Elsevier eBooks · doi:10.1016/b978-0-12-374135-6.00065-0
Lai, L. M., Moritani, T., Matsumoto, S., et al. (2021) · Springer eBooks · doi:10.1007/978-3-030-62120-9_19
(2009) · Springer eBooks · doi:10.1007/978-3-540-78785-3_14
Sohn, J., Bannerman, P. G. C., Guo, F., Burns, T., Miers, L. A., Croteau, C., Singhal, N. K., McDonough, J. A., & Pleasure, D. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2013-16.2017
Therapeutic strategies based on genetic interventions
Baek, R. C., Finn, P. F., & Martini, P. G. V. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99417-0.00013-6
10.1016/b978-1-4557-7485-2.00161-2
(2000) · Time to knit · doi:10.1016/b978-1-4557-7485-2.00161-2
Rahimian, E., Tahsini, M. R., Karimzadeh, P., et al. (2026) · Brain and Development · doi:10.1016/j.braindev.2026.104564
Diagnostic value of quantitative MR spectroscopy metabolite ratios for Canavan disease
Tahsini, M. R., Wylezinska‐Arridge, M., Zare, M., et al. (2026) · Frontiers in Radiology · doi:10.3389/fradi.2026.1826170
“CD has a pathognomonic appearance on 1H-MRS, characterized by marked, isolated increase of the NAA peak (9).”
InfluentialMagnetic resonance imaging in leukodystrophies: characteristic patterns and diagnostic relevance
Ruffini, M. D. L., Pereira, D. D. A., Helmer, R. S., de Souza, A. M., Lima, B. S., Baccarin, G., Yamada, G. K., Borella, L. F. M., Turci, R. D., Duarte, J. Á., et al. (2026) · Arquivos de Neuro-Psiquiatria · doi:10.1055/s-0046-1824758
“37,38 Analysis of MRI is highly characteristic, showing bilateral, symmetric T2/FLAIR hyperintensity of subcortical white matter — most marked frontally and parietally — with early globus-pallidus and thalamic involvement and, unlike many leukodystrophies, no sparing of U-fi bers or contrast…”
Rahman, S. M., Peng, A., Si, K., Kenny-Howell, C. L., Singh, M., Asif, M. A., Rahman, S. Z., Rahmani, S., Pasquini, L., Adin, M. E., et al. (2026) · The Neuroradiology Journal · doi:10.1177/19714009261487613
“These findings are best appreciated in white matter using SVS or MVS. 84,85 Maple syrup urine disease (MSUD).”
- Authors
- Janson, C., McPhee, S., Francis, J., Shera, D., Assadi, M., Freese, A., Hurh, P., Haselgrove, J., Wang, D., Bilaniuk, L., & Leone, P.
- Affiliations
- Children's Hospital of Philadelphia (US)
- University of Minnesota (US)
- Venue
- Neuropediatrics
- Publisher
- Georg Thieme Verlag KG
- Published
- 2006-08
- Volume
- 37
- Issue
- 4
- Pages
- 209-221
- ISSN
- 0174-304X (ISSN-L)
- 1439-1899
- OpenAlex
- W1994486944
- Cited by
- 82
- References
- 0
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 6 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 10
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropediatrics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- Canavan disease, leukodystrophy, aspartoacylase deficiency, N-acetylaspartate, natural history (disease), disease progression, white matter, gray matter, fractional anisotropy, apparent diffusion coefficient, quantitative T1 mapping, 1H NMR, diffusion-weighted imaging, longitudinal neuroimaging
- MeSH terms
- Age Factors, Aspartic Acid, Atrophy, Brain, Child, Preschool, Dipeptides, Female, Humans, Infant, Male, Magnetic Resonance Spectroscopy, Protons, Reference Values, Confidence Intervals, Case-Control Studies, Canavan Disease, Diffusion Magnetic Resonance Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
