Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease
Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson’s disease (PD) known so far. Substantia nigra (SN) hyperechogenicity, a sonographic...
Gespeichert in:
| Veröffentlicht in: | Journal of neurology 2013-10, Vol.260 (10), p.2523-2531 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2531 |
|---|---|
| container_issue | 10 |
| container_start_page | 2523 |
| container_title | Journal of neurology |
| container_volume | 260 |
| creator | Böttcher, Tobias Rolfs, Arndt Meyer, Bianca Grossmann, Annette Berg, Daniela Kropp, Peter Benecke, Reiner Walter, Uwe |
| description | Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson’s disease (PD) known so far.
Substantia nigra
(SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %;
p
|
| doi_str_mv | 10.1007/s00415-013-7011-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1443397484</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1443397484</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-4b5936068339d4570737e7daf242ebe5668136706772d0bde248c6c5fd909fbd3</originalsourceid><addsrcrecordid>eNp1kc9O3DAQxq2qqLulfQAulaVeOGxg_CdxckQruq20EhzgbDn2ZDFkncVODtz6Gn09nqReLVQVEqeRZn7fN6P5CDlhcMYA1HkCkKwsgIlCAWMF_0DmTApeMFk2H8kchISiFKWckc8p3QNAnQefyIyLmrGmqucEl70P3pp-QTcYcPR2QU1wtI3GB5qGMGyi2d15Szs04xQx0Yi9GdHRcaDXJj74kKnn338SdT6hSUizcGUme4fxtfWFHHWmT_j1pR6T2x-XN8ufxfpq9Wt5sS6sUHwsZFs2ooKqFqJxslSghELlTMclxxbLqqqZqBRUSnEHrUMua1vZsnMNNF3rxDE5Pfju4vA4YRr11ieLfW8CDlPSTMpsrWQtM_r9DXo_TDHk6_YU41wJyTLFDpSNQ0oRO72Lfmvik2ag9xnoQwY6Z6D3GWieNd9enKd2i-6f4vXpGeAHIOVR2GD8b_W7rn8BLQSRFw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1441227341</pqid></control><display><type>article</type><title>Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease</title><source>MEDLINE</source><source>SpringerLink</source><creator>Böttcher, Tobias ; Rolfs, Arndt ; Meyer, Bianca ; Grossmann, Annette ; Berg, Daniela ; Kropp, Peter ; Benecke, Reiner ; Walter, Uwe</creator><creatorcontrib>Böttcher, Tobias ; Rolfs, Arndt ; Meyer, Bianca ; Grossmann, Annette ; Berg, Daniela ; Kropp, Peter ; Benecke, Reiner ; Walter, Uwe</creatorcontrib><description>Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson’s disease (PD) known so far.
Substantia nigra
(SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %;
p
< 0.001,
p
< 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN
pars compacta
, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD,
n
= 4; early PD,
n
= 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.</description><identifier>ISSN: 0340-5354</identifier><identifier>EISSN: 1432-1459</identifier><identifier>DOI: 10.1007/s00415-013-7011-2</identifier><identifier>PMID: 23811968</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Brain - pathology ; Constipation ; Disease ; DNA Mutational Analysis ; Enzyme Replacement Therapy ; Female ; Gaucher Disease - complications ; Gaucher Disease - diagnostic imaging ; Gaucher Disease - genetics ; Gaucher Disease - therapy ; Glucosylceramidase - metabolism ; Health risk assessment ; Humans ; Iron ; Kinases ; Magnetic Resonance Imaging ; Male ; Medicine ; Medicine & Public Health ; Mental depression ; Middle Aged ; Mutation ; Mutation - genetics ; Neurodegeneration ; Neurology ; Neuroradiology ; Neurosciences ; Olfaction disorders ; Original Communication ; Parkinson Disease - complications ; Parkinson Disease - diagnostic imaging ; Parkinson Disease - genetics ; Parkinson Disease - therapy ; Parkinson's disease ; Patients ; Severity of Illness Index ; Statistics, Nonparametric ; Ultrasonic imaging ; Ultrasonography, Doppler, Transcranial ; Young Adult</subject><ispartof>Journal of neurology, 2013-10, Vol.260 (10), p.2523-2531</ispartof><rights>Springer-Verlag Berlin Heidelberg 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-4b5936068339d4570737e7daf242ebe5668136706772d0bde248c6c5fd909fbd3</citedby><cites>FETCH-LOGICAL-c372t-4b5936068339d4570737e7daf242ebe5668136706772d0bde248c6c5fd909fbd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00415-013-7011-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00415-013-7011-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23811968$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Böttcher, Tobias</creatorcontrib><creatorcontrib>Rolfs, Arndt</creatorcontrib><creatorcontrib>Meyer, Bianca</creatorcontrib><creatorcontrib>Grossmann, Annette</creatorcontrib><creatorcontrib>Berg, Daniela</creatorcontrib><creatorcontrib>Kropp, Peter</creatorcontrib><creatorcontrib>Benecke, Reiner</creatorcontrib><creatorcontrib>Walter, Uwe</creatorcontrib><title>Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease</title><title>Journal of neurology</title><addtitle>J Neurol</addtitle><addtitle>J Neurol</addtitle><description>Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson’s disease (PD) known so far.
Substantia nigra
(SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %;
p
< 0.001,
p
< 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN
pars compacta
, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD,
n
= 4; early PD,
n
= 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.</description><subject>Adult</subject><subject>Aged</subject><subject>Brain - pathology</subject><subject>Constipation</subject><subject>Disease</subject><subject>DNA Mutational Analysis</subject><subject>Enzyme Replacement Therapy</subject><subject>Female</subject><subject>Gaucher Disease - complications</subject><subject>Gaucher Disease - diagnostic imaging</subject><subject>Gaucher Disease - genetics</subject><subject>Gaucher Disease - therapy</subject><subject>Glucosylceramidase - metabolism</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Iron</subject><subject>Kinases</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental depression</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Neurodegeneration</subject><subject>Neurology</subject><subject>Neuroradiology</subject><subject>Neurosciences</subject><subject>Olfaction disorders</subject><subject>Original Communication</subject><subject>Parkinson Disease - complications</subject><subject>Parkinson Disease - diagnostic imaging</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson Disease - therapy</subject><subject>Parkinson's disease</subject><subject>Patients</subject><subject>Severity of Illness Index</subject><subject>Statistics, Nonparametric</subject><subject>Ultrasonic imaging</subject><subject>Ultrasonography, Doppler, Transcranial</subject><subject>Young Adult</subject><issn>0340-5354</issn><issn>1432-1459</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc9O3DAQxq2qqLulfQAulaVeOGxg_CdxckQruq20EhzgbDn2ZDFkncVODtz6Gn09nqReLVQVEqeRZn7fN6P5CDlhcMYA1HkCkKwsgIlCAWMF_0DmTApeMFk2H8kchISiFKWckc8p3QNAnQefyIyLmrGmqucEl70P3pp-QTcYcPR2QU1wtI3GB5qGMGyi2d15Szs04xQx0Yi9GdHRcaDXJj74kKnn338SdT6hSUizcGUme4fxtfWFHHWmT_j1pR6T2x-XN8ufxfpq9Wt5sS6sUHwsZFs2ooKqFqJxslSghELlTMclxxbLqqqZqBRUSnEHrUMua1vZsnMNNF3rxDE5Pfju4vA4YRr11ieLfW8CDlPSTMpsrWQtM_r9DXo_TDHk6_YU41wJyTLFDpSNQ0oRO72Lfmvik2ag9xnoQwY6Z6D3GWieNd9enKd2i-6f4vXpGeAHIOVR2GD8b_W7rn8BLQSRFw</recordid><startdate>20131001</startdate><enddate>20131001</enddate><creator>Böttcher, Tobias</creator><creator>Rolfs, Arndt</creator><creator>Meyer, Bianca</creator><creator>Grossmann, Annette</creator><creator>Berg, Daniela</creator><creator>Kropp, Peter</creator><creator>Benecke, Reiner</creator><creator>Walter, Uwe</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20131001</creationdate><title>Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease</title><author>Böttcher, Tobias ; Rolfs, Arndt ; Meyer, Bianca ; Grossmann, Annette ; Berg, Daniela ; Kropp, Peter ; Benecke, Reiner ; Walter, Uwe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-4b5936068339d4570737e7daf242ebe5668136706772d0bde248c6c5fd909fbd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Brain - pathology</topic><topic>Constipation</topic><topic>Disease</topic><topic>DNA Mutational Analysis</topic><topic>Enzyme Replacement Therapy</topic><topic>Female</topic><topic>Gaucher Disease - complications</topic><topic>Gaucher Disease - diagnostic imaging</topic><topic>Gaucher Disease - genetics</topic><topic>Gaucher Disease - therapy</topic><topic>Glucosylceramidase - metabolism</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Iron</topic><topic>Kinases</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mental depression</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Neurodegeneration</topic><topic>Neurology</topic><topic>Neuroradiology</topic><topic>Neurosciences</topic><topic>Olfaction disorders</topic><topic>Original Communication</topic><topic>Parkinson Disease - complications</topic><topic>Parkinson Disease - diagnostic imaging</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson Disease - therapy</topic><topic>Parkinson's disease</topic><topic>Patients</topic><topic>Severity of Illness Index</topic><topic>Statistics, Nonparametric</topic><topic>Ultrasonic imaging</topic><topic>Ultrasonography, Doppler, Transcranial</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Böttcher, Tobias</creatorcontrib><creatorcontrib>Rolfs, Arndt</creatorcontrib><creatorcontrib>Meyer, Bianca</creatorcontrib><creatorcontrib>Grossmann, Annette</creatorcontrib><creatorcontrib>Berg, Daniela</creatorcontrib><creatorcontrib>Kropp, Peter</creatorcontrib><creatorcontrib>Benecke, Reiner</creatorcontrib><creatorcontrib>Walter, Uwe</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Böttcher, Tobias</au><au>Rolfs, Arndt</au><au>Meyer, Bianca</au><au>Grossmann, Annette</au><au>Berg, Daniela</au><au>Kropp, Peter</au><au>Benecke, Reiner</au><au>Walter, Uwe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease</atitle><jtitle>Journal of neurology</jtitle><stitle>J Neurol</stitle><addtitle>J Neurol</addtitle><date>2013-10-01</date><risdate>2013</risdate><volume>260</volume><issue>10</issue><spage>2523</spage><epage>2531</epage><pages>2523-2531</pages><issn>0340-5354</issn><eissn>1432-1459</eissn><abstract>Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson’s disease (PD) known so far.
Substantia nigra
(SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %;
p
< 0.001,
p
< 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN
pars compacta
, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD,
n
= 4; early PD,
n
= 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>23811968</pmid><doi>10.1007/s00415-013-7011-2</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-5354 |
| ispartof | Journal of neurology, 2013-10, Vol.260 (10), p.2523-2531 |
| issn | 0340-5354 1432-1459 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1443397484 |
| source | MEDLINE; SpringerLink |
| subjects | Adult Aged Brain - pathology Constipation Disease DNA Mutational Analysis Enzyme Replacement Therapy Female Gaucher Disease - complications Gaucher Disease - diagnostic imaging Gaucher Disease - genetics Gaucher Disease - therapy Glucosylceramidase - metabolism Health risk assessment Humans Iron Kinases Magnetic Resonance Imaging Male Medicine Medicine & Public Health Mental depression Middle Aged Mutation Mutation - genetics Neurodegeneration Neurology Neuroradiology Neurosciences Olfaction disorders Original Communication Parkinson Disease - complications Parkinson Disease - diagnostic imaging Parkinson Disease - genetics Parkinson Disease - therapy Parkinson's disease Patients Severity of Illness Index Statistics, Nonparametric Ultrasonic imaging Ultrasonography, Doppler, Transcranial Young Adult |
| title | Clinical, genetic, and brain sonographic features related to Parkinson’s disease in Gaucher disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T18%3A24%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clinical,%20genetic,%20and%20brain%20sonographic%20features%20related%20to%20Parkinson%E2%80%99s%20disease%20in%20Gaucher%20disease&rft.jtitle=Journal%20of%20neurology&rft.au=B%C3%B6ttcher,%20Tobias&rft.date=2013-10-01&rft.volume=260&rft.issue=10&rft.spage=2523&rft.epage=2531&rft.pages=2523-2531&rft.issn=0340-5354&rft.eissn=1432-1459&rft_id=info:doi/10.1007/s00415-013-7011-2&rft_dat=%3Cproquest_cross%3E1443397484%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1441227341&rft_id=info:pmid/23811968&rfr_iscdi=true |