Alberto Bizzi

Magnetic resonance imaging pattern recognition in hypomyelinating disorders.

Hypomyelination is observed in the context of a growing number of genetic disorders that share clinical characteristics. The aim of this study was to determine the possible role of magnetic resonance imaging pattern recognition in distinguishing different hypomyelinating disorders, which would facilitate the diagnostic process. Only patients with hypomyelination of known cause were included in this retrospective study. A total of 112 patients with Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, Pelizaeus-Merzbacher-like disease, infantile GM1 and GM2 gangliosidosis, Salla disease and fucosidosis were included. The brain scans were rated using a standard scoring list; the raters were blinded to the diagnoses. Grouping of the patients was based on cluster analysis. Ten clusters of patients with similar magnetic resonance imaging abnormalities were identified. The most important discriminating items were early cerebellar atrophy, homogeneity of the white matter signal on T(2)-weighted images, abnormal signal intensity of the basal ganglia, signal abnormalities in the pons and additional T(2) lesions in the deep white matter. Eight clusters each represented mainly a single disorder (i.e. Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, infantile GM1 and GM2 gangliosidosis, Pelizaeus-Merzbacher-like disease and fucosidosis); only two clusters contained multiple diseases. Pelizaeus-Merzbacher-like disease was divided between two clusters and Salla disease did not cluster at all. This study shows that it is possible to separate patients with hypomyelination disorders of known cause in clusters based on magnetic resonance imaging abnormalities alone. In most cases of Pelizaeus-Merzbacher disease, hypomyelination with congenital cataract, hypomyelination with hypogonadotropic hypogonadism and hypodontia, Pelizaeus-Merzbacher-like disease, infantile GM1 and GM2 gangliosidosis and fucosidosis, the imaging pattern gives clues for the diagnosis.

Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations

Recessive mutations in GJA12/GJC2, the gene that encodes the gap junction protein connexin47 (Cx47), cause Pelizaeus-Merzbacher-like disease (PMLD), an early onset dysmyelinating disorder of the CNS, characterized by nystagmus, psychomotor delay, progressive spasticity and cerebellar signs. Here we describe three patients from one family with a novel recessively inherited mutation, 99C>G (predicted to cause an Ile>Met amino acid substitution; I33M) that causes a milder phenotype. All three had a late-onset, slowly progressive, complicated spastic paraplegia, with normal or near-normal psychomotor development, preserved walking capability through adulthood, and no nystagmus. MRI and MR spectroscopy imaging were consistent with a hypomyelinating leukoencephalopathy. The mutant protein forms gap junction plaques at cell borders similar to wild-type (WT) Cx47 in transfected cells, but fails to form functional homotypic channels in scrape-loading and dual whole-cell patch clamp assays. I33M forms overlapping gap junction plaques and functional channels with Cx43, however, I33M/Cx43 channels open only when a large voltage difference is applied to paired cells. These channels probably do not function under physiological conditions, suggesting that Cx47/Cx43 channels between astrocytes and oligodendrocytes are disrupted, similar to the loss-of-function endoplasmic reticulum-retained Cx47 mutants that cause PMLD. Thus, GJA12/GJC2 mutations can result in a milder phenotype than previously appreciated, but whether I33M retains a function of Cx47 not directly related to forming functional gap junction channels is not known.

GJA12 mutations in children with recessive hypomyelinating leukoencephalopathy

Background: Pelizaeus-Merzbacher-like disease (PMLD) is an inherited hypomyelinating leukoencephalopathy with onset in early infancy. Like Pelizaeus-Merzbacher disease (PMD), PMLD is characterized clinically by nystagmus, cerebellar ataxia, and spasticity, due to a permanent lack of myelin deposition in the brain. Mutations in the GJA12 gene, encoding connexin 47 (Cx47), were recently reported in five children with autosomal recessive PMLD. Objectives: To evaluate the impact of mutations in the GJA12 gene in, and define the clinical and neuroimaging features of, autosomal recessive PMLD. Results: The authors screened for GJA12 mutations in 10 additional PMLD families originating from Italy, Pakistan, and Saudi Arabia. Three novel homozygous GJA12 mutations were identified in 12 mutant cases distributed in 3 of 10 families. The mutations segregated with the disease according to an autosomal recessive trait and included one missense (G236S) and two nonsense (L281fs285X and P131fs144X) changes. Conclusions: The identification of homozygous mutations predicting the synthesis of aberrant and truncated polypeptides, and their tight segregation with the disease in very large families, clearly demonstrate that the loss of Cx47 function is the cause of the disease. The phenotype of GJA12-related Pelizaeus-Merzbacher-like disease is fairly homogeneous and similar to that of Pelizaeus-Merzbacher disease. However, slower progression of symptoms, greater preservation of cognitive functions, and partial myelination of corticospinal tracts at MRI were distinctive features, which could help in the differential diagnosis.

X‐linked creatine deficiency syndrome: A novel mutation in creatine transporter gene SLC6A8

Among creatine deficiency syndromes, an X‐linked condition related to a defective creatine transport into the central nervous system has been described recently. Hallmarks of the disease are the absence of a creatine signal at brain spectroscopy, increased creatine levels in blood and urine, ineffectiveness of oral supplementation, and a mutation in the SLC6A8 (Online Mendelian Inheritance in Man [OMIM] 300036) creatine transporter gene. We report on a patient in whom a novel mutation (1221‐1223delTTC) was identified.

Effects of riboflavin in children with complex II deficiency

Isolated complex II deficiency is a rare cause of mitochondrial disease in infancy and childhood. No satisfactory treatment is currently available, and affected patients undergo a relentlessly progressive motor and mental deterioration. We report on three complex II-deficient children treated with riboflavin per os, who were followed-up for a mean period of 4.5 years. In two patients with early-onset leukoencephalopathy, neurological condition remained stable or even moderately improved. In the third child, presenting in the first year of life with poor somatic growth and severe hyperlactacidemia, plasma lactate decreased to near-normal levels, and he did not develop signs of neurological involvement. Riboflavin supplementation to the growth medium of cultured fibroblasts resulted in a 2-fold increase of complex II activity in patients, but not in controls.

Clinical MR spectroscopy : techniques and applications

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Brainstem encephalitis resulting from Epstein-Barr virus mimicking an infiltrating tumor in a child

A case of a child with subacute neurologic features and imaging findings consistent with a brainstem encephalitis that was discovered to be related to a primary central nervous system infection caused by Epstein-Barr virus is presented. A brainstem tumor was initially suspected, but a correct diagnosis was formulated on the basis of the favorable clinical course and the detection of positive Epstein-Barr virus serology. In contrast to a prompt recovery of neurologic signs the neuroimaging alterations persisted for a longer time. The present report emphasizes the possible role of Epstein-Barr virus in the pathogenesis of infectious neurologic disorders in childhood, underlining the unusual presentation of a brainstem encephalitis, and considers the discrepancy between the course of neurologic features and the evolution of imaging alterations.

Clinical MR Spectroscopy: Contents

clinical mr spectroscopy: techniques and applications clinical mr spectroscopy techniques and applications clinical mr spectroscopy techniques and applications clinical mr spectroscopy techniques and applications ebook clinical mr spectroscopy techniques and applications 1h mr spectroscopy: clinical applications universität bern clinical proton mr spectroscopy in central nervous system techniques and applications assets clinical mr neuroimaging: diffusion, perfusion and clinical mr neuroimagingdiffusion perfusion and functional mri: techniques and applications magnetic resonance spectroscopy and its clinical the value of proton mr spectroscopy in pediatric metabolic current and potential applications of clinical 13c mr magnetic resonance spectroscopy of the breast workshop magnetic resonance spectroscopy in vivo magnetic resonance spectroscopy: is it ripe for clinical clinical applications of proton mr spectroscopy in the magnetic resonance spectroscopy mrs for evaluation of appendix e1: technical considerations for clinical mr oncological applications of mr spectroscopy crcnetbase advanced magnetic resonance techniques in neuroimaging introduction to clinical in vivo mr spectroscopy advanced mr techniques in brain tumor imaging cardiac spectroscopy: techniques, indications and clinical in vivo nmr spectroscopy principles and techniques faae clinical applications of magnetic resonance spectroscopy cardiac magnetic resonance spectroscopy: potential syllabus mr course 051617 physics & astronomy clinical magnetic resonance spectroscopy link.springer neuroradiology: using mr spectroscopy and perfusion 4712-103t release date advanced mri neurological applications functional mri basic principles and clinical applications basic principles and clinical applications of magnetic nmr spectroscopy explained simplified theory applications clinical application of in vivo proton ( mr spectroscopy magnetic resonance spectroscopy (mrs) and its application future potential clinical applications of spectroscopic advanced mr methods at ultra-high field (7 tesla) for techniques and physics the university of edinburgh 7 tesla clinical applications in msk siegfried trattnig clinical mr spectroscopy first principles high field mri: technology, applications, safety, and

Clinical MR Spectroscopy: Abbreviations

clinical mr spectroscopy: techniques and applications clinical mr spectroscopy techniques and applications clinical mr spectroscopy techniques and applications clinical mr spectroscopy techniques and applications ebook clinical mr spectroscopy techniques and applications 1h mr spectroscopy: clinical applications universität bern clinical proton mr spectroscopy in central nervous system techniques and applications assets clinical mr neuroimaging: diffusion, perfusion and clinical mr neuroimagingdiffusion perfusion and functional mri: techniques and applications magnetic resonance spectroscopy and its clinical the value of proton mr spectroscopy in pediatric metabolic current and potential applications of clinical 13c mr magnetic resonance spectroscopy of the breast workshop magnetic resonance spectroscopy in vivo magnetic resonance spectroscopy: is it ripe for clinical clinical applications of proton mr spectroscopy in the magnetic resonance spectroscopy mrs for evaluation of appendix e1: technical considerations for clinical mr oncological applications of mr spectroscopy crcnetbase advanced magnetic resonance techniques in neuroimaging introduction to clinical in vivo mr spectroscopy advanced mr techniques in brain tumor imaging cardiac spectroscopy: techniques, indications and clinical in vivo nmr spectroscopy principles and techniques faae clinical applications of magnetic resonance spectroscopy cardiac magnetic resonance spectroscopy: potential syllabus mr course 051617 physics & astronomy clinical magnetic resonance spectroscopy link.springer neuroradiology: using mr spectroscopy and perfusion 4712-103t release date advanced mri neurological applications functional mri basic principles and clinical applications basic principles and clinical applications of magnetic nmr spectroscopy explained simplified theory applications clinical application of in vivo proton ( mr spectroscopy magnetic resonance spectroscopy (mrs) and its application future potential clinical applications of spectroscopic advanced mr methods at ultra-high field (7 tesla) for techniques and physics the university of edinburgh 7 tesla clinical applications in msk siegfried trattnig clinical mr spectroscopy first principles high field mri: technology, applications, safety, and

Clinical MR Spectroscopy: Frontmatter

clinical mr spectroscopy: techniques and applications clinical mr spectroscopy techniques and applications clinical mr spectroscopy techniques and applications clinical mr spectroscopy techniques and applications ebook clinical mr spectroscopy techniques and applications 1h mr spectroscopy: clinical applications universität bern clinical proton mr spectroscopy in central nervous system techniques and applications assets clinical mr neuroimaging: diffusion, perfusion and clinical mr neuroimagingdiffusion perfusion and functional mri: techniques and applications magnetic resonance spectroscopy and its clinical the value of proton mr spectroscopy in pediatric metabolic current and potential applications of clinical 13c mr magnetic resonance spectroscopy of the breast workshop magnetic resonance spectroscopy in vivo magnetic resonance spectroscopy: is it ripe for clinical clinical applications of proton mr spectroscopy in the magnetic resonance spectroscopy mrs for evaluation of appendix e1: technical considerations for clinical mr oncological applications of mr spectroscopy crcnetbase advanced magnetic resonance techniques in neuroimaging introduction to clinical in vivo mr spectroscopy advanced mr techniques in brain tumor imaging cardiac spectroscopy: techniques, indications and clinical in vivo nmr spectroscopy principles and techniques faae clinical applications of magnetic resonance spectroscopy cardiac magnetic resonance spectroscopy: potential syllabus mr course 051617 physics & astronomy clinical magnetic resonance spectroscopy link.springer neuroradiology: using mr spectroscopy and perfusion 4712-103t release date advanced mri neurological applications functional mri basic principles and clinical applications basic principles and clinical applications of magnetic nmr spectroscopy explained simplified theory applications clinical application of in vivo proton ( mr spectroscopy magnetic resonance spectroscopy (mrs) and its application future potential clinical applications of spectroscopic advanced mr methods at ultra-high field (7 tesla) for techniques and physics the university of edinburgh 7 tesla clinical applications in msk siegfried trattnig clinical mr spectroscopy first principles high field mri: technology, applications, safety, and