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Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations
Pelizaeus‐Merzbacher disease (PMD) is an X‐linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve pati...
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Published in: | Journal of neuroscience research 2014-12, Vol.92 (12), p.1723-1732 |
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description | Pelizaeus‐Merzbacher disease (PMD) is an X‐linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age‐matched controls. The parallel (λ//), perpendicular (λ⊥), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥. In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥. These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ//, are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc. |
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We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age‐matched controls. The parallel (λ//), perpendicular (λ⊥), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥. In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥. These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ//, are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.</description><identifier>ISSN: 0360-4012</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.23458</identifier><identifier>PMID: 25156430</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Brain - pathology ; Cerebral Peduncle - pathology ; Child ; Child, Preschool ; CNS ; Corpus Callosum - pathology ; Diffusion ; Diffusion Tensor Imaging ; Disability Evaluation ; DT-MRI ; Humans ; Internal Capsule - pathology ; Magnetic Resonance Imaging ; Male ; Medical research ; Middle Aged ; Mutation ; Mutation - genetics ; myelin ; Myelin Proteolipid Protein - genetics ; Pelizaeus-Merzbacher disease ; Pelizaeus-Merzbacher Disease - genetics ; Pelizaeus-Merzbacher Disease - pathology ; White Matter - pathology ; Young Adult</subject><ispartof>Journal of neuroscience research, 2014-12, Vol.92 (12), p.1723-1732</ispartof><rights>2014 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4948-7f9d32662ad74014899c353b45dd8332dba9113287870452c782af0ba2f942d43</citedby><cites>FETCH-LOGICAL-c4948-7f9d32662ad74014899c353b45dd8332dba9113287870452c782af0ba2f942d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25156430$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Laukka, Jeremy J.</creatorcontrib><creatorcontrib>Makki, Malek I.</creatorcontrib><creatorcontrib>Lafleur, Tori</creatorcontrib><creatorcontrib>Stanley, Jeffrey</creatorcontrib><creatorcontrib>Kamholz, John</creatorcontrib><creatorcontrib>Garbern, James Y.</creatorcontrib><title>Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations</title><title>Journal of neuroscience research</title><addtitle>Journal of Neuroscience Research</addtitle><description>Pelizaeus‐Merzbacher disease (PMD) is an X‐linked disorder of the central nervous system (CNS) caused by a wide variety of mutations affecting proteolipid protein 1 (PLP1). We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age‐matched controls. The parallel (λ//), perpendicular (λ⊥), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥. In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥. These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ//, are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Brain - pathology</subject><subject>Cerebral Peduncle - pathology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>CNS</subject><subject>Corpus Callosum - pathology</subject><subject>Diffusion</subject><subject>Diffusion Tensor Imaging</subject><subject>Disability Evaluation</subject><subject>DT-MRI</subject><subject>Humans</subject><subject>Internal Capsule - pathology</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>myelin</subject><subject>Myelin Proteolipid Protein - genetics</subject><subject>Pelizaeus-Merzbacher disease</subject><subject>Pelizaeus-Merzbacher Disease - genetics</subject><subject>Pelizaeus-Merzbacher Disease - pathology</subject><subject>White Matter - pathology</subject><subject>Young Adult</subject><issn>0360-4012</issn><issn>1097-4547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNqN0U9PFDEYBvCGaGBBDnwB0sSLHgbe_p8ezaqo2SzEKByb7kxn7Trbru1MgG9vcYCDiYmn9vB7n7ztg9AJgTMCQM83IZ1RxkW9h2YEtKq44OoFmgGTUHEg9AAd5rwBAK0F20cHVBAhOYMZWr73XTdmHwMeXMgxYb-1ax_WOHZ4ZwfvwpDxrR9-4F2Kg4u93_l2uvuACV674PB2HAqNIb9CLzvbZ3f8eB6h7x8_fJt_qhaXF5_n7xZVwzWvK9XpllEpqW1V2Y_XWjdMsBUXbVszRtuV1YQwWqtaARe0UTW1Haws7TSnLWdH6M2UWxb5Nbo8mK3Pjet7G1wcsyGSUkm4BvEflDDNpWBQ6Ou_6CaOKZSHPCgqawpcF_V2Uk2KOSfXmV0qn5buDQHz0IcpfZg_fRR7-pg4rraufZZPBRRwPoFb37v7fyeZL8uvT5HVNOHz4O6eJ2z6aaRiSpib5YWZ0-UNW7Brc8V-A5n9oR4</recordid><startdate>201412</startdate><enddate>201412</enddate><creator>Laukka, Jeremy J.</creator><creator>Makki, Malek I.</creator><creator>Lafleur, Tori</creator><creator>Stanley, Jeffrey</creator><creator>Kamholz, John</creator><creator>Garbern, James Y.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>RC3</scope></search><sort><creationdate>201412</creationdate><title>Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations</title><author>Laukka, Jeremy J. ; 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We assessed the effects of PLP1 mutations on water diffusion in CNS white matter by using diffusion tensor imaging. Twelve patients with different PLP1 point mutations encompassing a range of clinical phenotypes were analyzed, and the results were compared with a group of 12 age‐matched controls. The parallel (λ//), perpendicular (λ⊥), and apparent diffusion coefficients (ADC) and fractional anisotropy were measured in both limbs of the internal capsule, the genu and splenium of corpus callosum, the base of the pons, and the cerebral peduncles. The mean ADC and λ⊥ in the PMD patient group were both significantly increased in all selected structures, except for the base of the pons, compared with controls. PMD patients with the most severe disease, however, had a significant increase of both λ// and λ⊥. In contrast, more mildly affected patients had much smaller changes in λ// and λ⊥. These data suggest that myelin, the structure responsible in part for the λ⊥ barrier, is the major site of disease pathogenesis in this heterogeneous group of patients. Axons, in contrast, the structures mainly responsible for λ//, are much less affected, except within the subgroup of patients with the most severe disease. Clinical disability in patients with PLP1 point mutation is thus likely determined by the extent of pathological involvement of both myelin and axons, with alterations of both structures causing the most severe disease. © 2014 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25156430</pmid><doi>10.1002/jnr.23458</doi><tpages>10</tpages></addata></record> |
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subjects | Adolescent Adult Brain - pathology Cerebral Peduncle - pathology Child Child, Preschool CNS Corpus Callosum - pathology Diffusion Diffusion Tensor Imaging Disability Evaluation DT-MRI Humans Internal Capsule - pathology Magnetic Resonance Imaging Male Medical research Middle Aged Mutation Mutation - genetics myelin Myelin Proteolipid Protein - genetics Pelizaeus-Merzbacher disease Pelizaeus-Merzbacher Disease - genetics Pelizaeus-Merzbacher Disease - pathology White Matter - pathology Young Adult |
title | Diffusion tensor imaging of patients with proteolipid protein 1 gene mutations |
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