title: Widespread inflammation in CLIPPERS syndrome indicated by autopsy and ultra-high-field 7T MRI.
abstract: OBJECTIVE
  To examine if there is widespread inflammation in the brain of patients with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome by using histology and ultra-high-field MRI at 7.0T.
  
  
  METHODS
  We performed a detailed neuropathologic examination in 4 cases, including 1 autopsy case, and studied 2 additional patients by MRI at 7.0T to examine (1) extension of inflammation to areas appearing normal on 3.0T MRI, (2) potential advantages of 7.0T MRI compared to 3.0T MRI in reflecting widespread inflammation, perivascular pathology, and axonal damage, and (3) the possibility of lymphoma.
  
  
  RESULTS
  In the autopsy case, perivascular inflammation dominated by CD4+ T cells was not only detected in the brainstem and cerebellum but also in brain areas with normal appearance on 3.0T MRI, including supratentorial regions and cranial nerve roots. There was no evidence of lymphoma in any of the 4 patients. The 7.0T MRI in clinical remission also revealed supratentorial lesions and perivascular pathology in vivo with contrast-enhancing lesions centered around a small venous vessel. Ultra-high-field MRI at 7.0T disclosed prominent T1 hypointensities in the brainstem, which were not seen on 3.0T MRI. This corresponded to neuropathologic detection of axonal injury in the autopsy case.
  
  
  CONCLUSIONS
  Our findings suggest more widespread perivascular inflammation and postinflammatory axonal injury in patients with CLIPPERS.
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Morten
authors.initials: M
authors.lastname: Blaabjerg
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Tim
authors.initials: T
authors.lastname: Sinnecker
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kondziella
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Thoralf
authors.initials: T
authors.lastname: Niendorf
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Bjørg Morell
authors.initials: BM
authors.lastname: Kerrn-Jespersen
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Mette
authors.initials: M
authors.lastname: Lindelof
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Bjarne Winther
authors.initials: BW
authors.lastname: Kristensen
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Departments of Neurology (M.B., Z.I.) and Pathology (B.W.K.), Odense University Hospital, Denmark; Clinical and Experimental Multiple Sclerosis Research Center (K.R., T.S., F.P.), Department of Neurology (K.R., F.P.), NeuroCure Clinical Research Center (T.S., F.P.), and Experimental and Clinical Research Center (T.N., F.P.), Charité-Universitätsmedizin Berlin, Germany; Department of Neurology (T.S.), Universitatsspital Basel, Switzerland; Department of Neurology (D.K.), Rigshospitalet, Copenhagen University Hospital, Denmark; Berlin Ultrahigh Field Facility (B.U.F.F.) (T.N.), Max Delbrueck Center for Molecular Medicine (F.P.), Berlin, Germany; Department of Neurology (B.M.K.-J., M.L.), Herlev Hospital, Denmark; Center for Brain Research (H.L.), Medical University of Vienna, Austria; and Institute of Clinical Research (M.B., B.W.K., Z.I.), University of Southern Denmark, Odense.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes