Metz, Imke

[["dc.bibliographiccitation.firstpage","148"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Neurology"],["dc.bibliographiccitation.lastpage","158"],["dc.bibliographiccitation.volume","84"],["dc.contributor.author","Popescu, Bogdan F. G."],["dc.contributor.author","Guo, Yong"],["dc.contributor.author","Jentoft, Mark E."],["dc.contributor.author","Parisi, Joseph E."],["dc.contributor.author","Lennon, Vanda A."],["dc.contributor.author","Pittock, Sean J."],["dc.contributor.author","Weinshenker, Brian G."],["dc.contributor.author","Wingerchuk, Dean M."],["dc.contributor.author","Giannini, Caterina"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Shuster, Elizabeth A."],["dc.contributor.author","Carter, Jonathan"],["dc.contributor.author","Boyd, Clara D."],["dc.contributor.author","Clardy, Stacey Lynn"],["dc.contributor.author","Cohen, Bruce A."],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.date.accessioned","2018-11-07T10:02:13Z"],["dc.date.available","2018-11-07T10:02:13Z"],["dc.date.issued","2015"],["dc.description.abstract","Objective: To assess, in a surgical biopsy cohort of active demyelinating lesions, the diagnostic utility of aquaporin-4 (AQP4) immunohistochemistry in identifying neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) and describe pathologic features that should prompt AQP4 immunohistochemical analysis and AQP4-immunoglobulin G (IgG) serologic testing. Methods: This was a neuropathologic cohort study of 20 surgical biopsies (19 patients; 11 cord/9 brain), performed because of diagnostic uncertainty, interpreted as active demyelinating disease and containing 2 or more of the following additional features: tissue vacuolation, granulocytic infiltrates, or astrocyte injury. Results: AQP4 immunoreactivity was lost in 18 biopsies and increased in 2. Immunopathologic features of the AQP4 loss cohort were myelin vacuolation (18), dystrophic astrocytes and granulocytes (17), vascular hyalinization (16), macrophages containing glial fibrillary acid protein (GFAP)-positive debris (14), and Creutzfeldt-Peters cells (0). All 14 cases with available serum tested positive for AQP4-IgG after biopsy. Diagnosis at last follow-up was NMO/NMOSD (15) and longitudinally extensive transverse myelitis (1 each relapsing and single). Immunopathologic features of the AQP4 increased cohort were macrophages containing GFAP-positive debris and granulocytes (2), myelin vacuolation (1), dystrophic astrocytes (1), Creutzfeldt-Peters cells (1), and vascular hyalinization (1). Diagnosis at last follow-up was multiple sclerosis (MS) and both tested AQP4-IgG seronegative after biopsy. Conclusions: AQP4 immunohistochemistry with subsequent AQP4-IgG testing has diagnostic utility in identifying cases of NMO/NMOSD. This study highlights the importance of considering NMOSD in the differential diagnosis of tumefactive brain or spinal cord lesions. AQP4-IgG testing may avert biopsy and avoid ineffective therapies if these patients are erroneously treated for MS."],["dc.identifier.isi","000347996400012"],["dc.identifier.pmid","25503621"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38185"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1526-632X"],["dc.relation.issn","0028-3878"],["dc.title","Diagnostic utility of aquaporin-4 in the analysis of active demyelinating lesions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e1906"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Neurology"],["dc.bibliographiccitation.lastpage","e1913"],["dc.bibliographiccitation.volume","97"],["dc.contributor.author","Tobin, W. Oliver"],["dc.contributor.author","Kalinowska-Lyszczarz, Alicja"],["dc.contributor.author","Weigand, Stephen D."],["dc.contributor.author","Guo, Yong"],["dc.contributor.author","Tosakulwong, Nirubol"],["dc.contributor.author","Parisi, Joseph E."],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Frischer, Josa M."],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.date.accessioned","2021-12-01T09:22:30Z"],["dc.date.available","2021-12-01T09:22:30Z"],["dc.date.issued","2021"],["dc.description.abstract","Background and Objectives The goal of this work was to compare clinical characteristics across immunopathologic subtypes of patients with multiple sclerosis. Methods Immunopathologic subtyping was performed on specimens from 547 patients with biopsy- or autopsy-confirmed CNS demyelination. Results The frequency of immunopathologic subtypes was 23% for pattern I, 56% for pattern II, and 22% for pattern III. Immunopatterns were similar in terms of age at autopsy/biopsy (median age 41 years, range 4–83 years, p = 0.16) and proportion female (54%, p = 0.71). Median follow-up after symptom onset was 2.3 years (range 0–38 years). In addition to being overrepresented among autopsy cases (45% vs 19% in biopsy cohort, p < 0.001), index attack-related disability was higher in pattern III vs II (median Expanded Disability Status Scale score 4 vs 3, p = 0.02). Monophasic clinical course was more common in patients with pattern III than pattern I or II (59% vs 33% vs 32%, p < 0.001). Similarly, patients with pattern III pathology were likely to have progressive disease compared to patients with patterns I or II when followed up for ≥5 years (24% overall, p = 0.49), with no differences in long-term survival, despite a more fulminant attack presentation. Conclusion All 3 immunopatterns can be detected in active lesions, although they are found less frequently later into the disease due to the lower number of active lesions. Pattern III is associated with a more fulminant initial attack than either pattern I or II. Biopsied patients appear to have similar long-term outcomes regardless of their immunopatterns. Progressive disease is less associated with the initial immunopattern and suggests convergence into a final common pathway related to the chronically denuded axon."],["dc.description.abstract","Background and Objectives The goal of this work was to compare clinical characteristics across immunopathologic subtypes of patients with multiple sclerosis. Methods Immunopathologic subtyping was performed on specimens from 547 patients with biopsy- or autopsy-confirmed CNS demyelination. Results The frequency of immunopathologic subtypes was 23% for pattern I, 56% for pattern II, and 22% for pattern III. Immunopatterns were similar in terms of age at autopsy/biopsy (median age 41 years, range 4–83 years, p = 0.16) and proportion female (54%, p = 0.71). Median follow-up after symptom onset was 2.3 years (range 0–38 years). In addition to being overrepresented among autopsy cases (45% vs 19% in biopsy cohort, p < 0.001), index attack-related disability was higher in pattern III vs II (median Expanded Disability Status Scale score 4 vs 3, p = 0.02). Monophasic clinical course was more common in patients with pattern III than pattern I or II (59% vs 33% vs 32%, p < 0.001). Similarly, patients with pattern III pathology were likely to have progressive disease compared to patients with patterns I or II when followed up for ≥5 years (24% overall, p = 0.49), with no differences in long-term survival, despite a more fulminant attack presentation. Conclusion All 3 immunopatterns can be detected in active lesions, although they are found less frequently later into the disease due to the lower number of active lesions. Pattern III is associated with a more fulminant initial attack than either pattern I or II. Biopsied patients appear to have similar long-term outcomes regardless of their immunopatterns. Progressive disease is less associated with the initial immunopattern and suggests convergence into a final common pathway related to the chronically denuded axon."],["dc.identifier.doi","10.1212/WNL.0000000000012782"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94416"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","1526-632X"],["dc.relation.issn","0028-3878"],["dc.title","Clinical Correlation of Multiple Sclerosis Immunopathologic Subtypes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","MULTIPLE SCLEROSIS"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.contributor.author","Openshaw, Harry"],["dc.contributor.author","Garcia-Merino, Antonio"],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Freedman, Marc S."],["dc.contributor.author","Azzarelli, Biagio"],["dc.contributor.author","Kolar, Oldrich J."],["dc.contributor.author","Atkins, H. L."],["dc.contributor.author","Brueck, Wolfgang"],["dc.date.accessioned","2018-11-07T09:22:49Z"],["dc.date.available","2018-11-07T09:22:49Z"],["dc.date.issued","2006"],["dc.format.extent","S9"],["dc.identifier.isi","000241921400027"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29435"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.publisher.place","London"],["dc.relation.conference","22nd Congress of the European-Committee-for-the-Treatment-and-Resarch-in-Multiple-Sclerosis"],["dc.relation.eventlocation","Madrid, SPAIN"],["dc.relation.issn","1352-4585"],["dc.title","Multiple sclerosis pathology after autologous stem cell transplantation: ongoing demyelination and neurodegeneration despite suppressed inflammation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","728"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","738"],["dc.bibliographiccitation.volume","75"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Weigand, Stephen D."],["dc.contributor.author","Popescu, Bogdan F. G."],["dc.contributor.author","Frischer, Josa M."],["dc.contributor.author","Parisi, Joseph E."],["dc.contributor.author","Guo, Yong"],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.date.accessioned","2018-11-07T09:40:29Z"],["dc.date.available","2018-11-07T09:40:29Z"],["dc.date.issued","2014"],["dc.description.abstract","Objective: Multiple sclerosis (MS) lesions demonstrate immunopathological heterogeneity in patterns of demyelination. Previous cross-sectional studies reported immunopatterns of demyelination were identical among multiple active demyelinating lesions from the same individual, but differed between individuals, leading to the hypothesis of intraindividual pathological homogeneity and interindividual heterogeneity. Other groups suggested a time-dependent heterogeneity of lesions. The objective of our present study was to analyze tissue samples collected longitudinally to determine whether patterns of demyelination persist over time within a given patient. Methods: Archival tissue samples derived from patients with pathologically confirmed central nervous system inflammatory demyelinating disease who had undergone either diagnostic serial biopsy or biopsy followed by autopsy were analyzed immunohistochemically. The inclusion criteria consisted of the presence of early active demyelinating lesions-required for immunopattern classification-obtained from the same patient at 2 or more time points. Results: Among 1,321 surgical biopsies consistent with MS, 22 cases met the study inclusion criteria. Twenty-one patients (95%) showed a persistence of immunopathological patterns in tissue sampled from different time points. This persistence was demonstrated for all major patterns of demyelination. A single patient showed features suggestive of both pattern II and pattern III on biopsy, but only pattern II among all active lesions examined at autopsy. Interpretation: These findings continue to support the concept of patient-dependent immunopathological heterogeneity in early MS and suggest that the mechanisms and targets of tissue injury may differ among patient subgroups. These observations have potentially significant implications for individualized therapeutic approaches."],["dc.identifier.doi","10.1002/ana.24163"],["dc.identifier.isi","000337706100014"],["dc.identifier.pmid","24771535"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33519"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1531-8249"],["dc.relation.issn","0364-5134"],["dc.title","Pathologic Heterogeneity Persists in Early Active Multiple Sclerosis Lesions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","45"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","64"],["dc.bibliographiccitation.volume","134"],["dc.contributor.author","Popescu, Bogdan F. G."],["dc.contributor.author","Frischer, Josa M."],["dc.contributor.author","Webb, Samuel M."],["dc.contributor.author","Tham, Mylyne"],["dc.contributor.author","Adiele, Reginald C."],["dc.contributor.author","Robinson, Christopher A."],["dc.contributor.author","Fitz-Gibbon, Patrick D."],["dc.contributor.author","Weigand, Stephen D."],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Nehzati, Susan"],["dc.contributor.author","George, Graham N."],["dc.contributor.author","Pickering, Ingrid J."],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Hametner, Simon"],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Parisi, Joseph E."],["dc.contributor.author","Yong, Guo"],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.date.accessioned","2018-11-07T10:22:07Z"],["dc.date.available","2018-11-07T10:22:07Z"],["dc.date.issued","2017"],["dc.description.abstract","Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) in which oligodendrocytes, the CNS cells that stain most robustly for iron and myelin are the targets of injury. Metals are essential for normal CNS functioning, and metal imbalances have been linked to demyelination and neuro-degeneration. Using a multidisciplinary approach involving synchrotron techniques, iron histochemistry and immunohistochemistry, we compared the distribution and quantification of iron and zinc in MS lesions to the surrounding normal appearing and periplaque white matter, and assessed the involvement of these metals in MS lesion pathogenesis. We found that the distribution of iron and zinc is heterogeneous in MS plaques, and with few remarkable exceptions they do not accumulate in chronic MS lesions. We show that brain iron tends to decrease with increasing age and disease duration of MS patients; reactive astrocytes organized in large astrogliotic areas in a subset of smoldering and inactive plaques accumulate iron and safely store it in ferritin; a subset of smoldering lesions do not contain a rim of iron-loaded macrophages/microglia; and the iron content of shadow plaques varies with the stage of remyelination. Zinc in MS lesions was generally decreased, paralleling myelin loss. Iron accumulates concentrically in a subset of chronic inactive lesions suggesting that not all iron rims around MS lesions equate with smoldering plaques. Upon degeneration of iron-loaded microglia/macrophages, astrocytes may form an additional protective barrier that may prevent iron-induced oxidative damage."],["dc.identifier.doi","10.1007/s00401-017-1696-8"],["dc.identifier.isi","000403235900004"],["dc.identifier.pmid","28332093"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14717"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42219"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e90"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.contributor.author","Openshaw, Harry"],["dc.contributor.author","Garcia-Merino, Antonio"],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Freedman, Marc S."],["dc.contributor.author","Azzarelli, Biagio"],["dc.contributor.author","Kolar, Oldrich J."],["dc.contributor.author","Atkins, H. L."],["dc.contributor.author","Brueck, Wolfgang"],["dc.date.accessioned","2018-11-07T11:18:29Z"],["dc.date.available","2018-11-07T11:18:29Z"],["dc.date.issued","2008"],["dc.identifier.doi","10.1093/brain/awm181"],["dc.identifier.isi","000252903900002"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55045"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.title","Autologous hematopoietic stem cell transplantation: the glass seems to be half full for aggressive, early forms of MS and half empty for advanced MS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","12"],["dc.bibliographiccitation.journal","Multiple Sclerosis Journal"],["dc.bibliographiccitation.lastpage","13"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Pfeifenbring, Sabine"],["dc.contributor.author","Bunyan, Reem F."],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.contributor.author","Brueck, Wolfgang"],["dc.date.accessioned","2018-11-07T09:05:35Z"],["dc.date.available","2018-11-07T09:05:35Z"],["dc.date.issued","2012"],["dc.identifier.isi","000328702200008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25356"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.publisher.place","London"],["dc.relation.conference","28th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis"],["dc.relation.eventlocation","Lyon, FRANCE"],["dc.relation.issn","1477-0970"],["dc.relation.issn","1352-4585"],["dc.title","Axonal damage in inflammatory demyelinating lesions of paediatric patients"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Multiple Sclerosis Journal"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Pfeifenbring, Sabine"],["dc.contributor.author","Bunyan, Reem F."],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Gaertner, J."],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.contributor.author","Brueck, Wolfgang"],["dc.date.accessioned","2018-11-07T10:08:45Z"],["dc.date.available","2018-11-07T10:08:45Z"],["dc.date.issued","2016"],["dc.format.extent","67"],["dc.identifier.isi","000383267200107"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39527"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.publisher.place","London"],["dc.relation.eventlocation","London, ENGLAND"],["dc.relation.issn","1477-0970"],["dc.relation.issn","1352-4585"],["dc.title","Oligodendroglial damage and remyelination in paediatric multiple sclerosis lesions."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1254"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","1262"],["dc.bibliographiccitation.volume","130"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.contributor.author","Openshaw, Harry"],["dc.contributor.author","Garcia-Merino, Antonio"],["dc.contributor.author","Lassmann, Hans"],["dc.contributor.author","Freedman, Marc S."],["dc.contributor.author","Atkins, H. L."],["dc.contributor.author","Azzarelli, Biagio"],["dc.contributor.author","Kolar, Oldrich J."],["dc.contributor.author","Brueck, Wolfgang"],["dc.date.accessioned","2018-11-07T11:02:36Z"],["dc.date.available","2018-11-07T11:02:36Z"],["dc.date.issued","2007"],["dc.description.abstract","The present study analyses autopsy material from five multiple sclerosis patients who received autologous stem cell transplantation. A total of 53 white matter lesions were investigated using routine and immunohistochemical stainings to characterize the demyelinating activity, inflammatory infiltrates, acutely damaged axons and macrophages/microglial cells. We found evidence for ongoing active demyelination in all of the five patients. The inflammatory infiltrate within the lesions showed only very few T cells and CD8+ cytotoxic T cells dominated the T cell population. B cells and plasma cells were completely absent from the lesions. High numbers of acutely damaged axons were found in active lesion areas. Tissue injury was associated with activated macrophages/microglial cells. The present results indicate that ongoing demyelination and axonal degeneration exist despite pronounced immunosuppression. Our data parallel results from some of the clinical phase I/II studies showing continued clinical disease progression in multiple sclerosis patients with high expanded disability system scores despite autologous stem cell transplantation."],["dc.identifier.doi","10.1093/brain/awl370"],["dc.identifier.isi","000246293400010"],["dc.identifier.pmid","17293360"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51422"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.title","Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","655"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","667"],["dc.bibliographiccitation.volume","77"],["dc.contributor.author","Pfeifenbring, Sabine"],["dc.contributor.author","Bunyan, Reem F."],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Roever, Christian"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Gärtner, Jutta"],["dc.contributor.author","Lucchinetti, Claudia F."],["dc.contributor.author","Brueck, Wolfgang"],["dc.date.accessioned","2017-09-07T11:44:29Z"],["dc.date.available","2017-09-07T11:44:29Z"],["dc.date.issued","2015"],["dc.description.abstract","ObjectiveAxonal damage occurs early in multiple sclerosis (MS) and contributes to the degree of clinical disability. Children with MS more often show disabling and polyfocal neurological symptoms at disease onset than adults with MS. Thus, axonal damage may differ between pediatric and adult MS patients. MethodsWe analyzed axonal pathology in archival brain biopsy and autopsy samples from 19 children with early MS. Lesions were classified according to demyelinating activity and presence of remyelination. Axonal density and extent of acute axonal damage were assessed using Bielschowsky silver impregnation and immunohistochemistry for amyloid precursor protein (APP), respectively. Axonal injury was correlated with the inflammatory infiltrate as well as clinical characteristics. Results were compared with data from adult MS patients. ResultsAcute axonal damage was most extensive in early active demyelinating (EA) lesions of pediatric patients and correlated positively with the Expanded Disability Status Scale at attack leading to biopsy/autopsy. Comparison with 12 adult patients showed a 50% increase in the extent of acute axonal damage in EA lesions from children compared to adults, with the highest number of APP-positive spheroids found prior to puberty. The extent of acute axonal damage correlated positively with the number of lesional macrophages. Axonal density was reduced in pediatric lesions irrespective of the demyelinating activity or the presence of remyelination. Axonal reduction was similar between children and adults. InterpretationOur results provide evidence for more pronounced acute axonal damage in inflammatory demyelinating lesions from children compared to adults. Ann Neurol 2015;77:655-667"],["dc.identifier.doi","10.1002/ana.24364"],["dc.identifier.gro","3141935"],["dc.identifier.isi","000352102500010"],["dc.identifier.pmid","25612167"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2713"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.eissn","1531-8249"],["dc.relation.issn","0364-5134"],["dc.title","Extensive Acute Axonal Damage in Pediatric Multiple Sclerosis Lesions"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]