title: Uncompacted Myelin Lamellae and Nodal Ion Channel Disruption in POEMS Syndrome.
abstract: To elucidate the significance of uncompacted myelin lamellae (UML) and ion channel disruption at the nodes of Ranvier in the polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, we evaluated sural nerve biopsy specimens from 33 patients with POEMS syndrome and from 7 control patients. Uncompacted myelin lamellae distribution was assessed by electron microscopy and immunofluorescence microscopy. In the POEMS patient biopsies, UML were seen more frequently in small versus large myelinated fibers. Paranodes and Schmidt-Lanterman incisures, where normal physiologic UM is located, were frequently associated with UM. Widening of the nodes of Ranvier (i.e. segmental demyelination) was not associated with UML. There was axonal hollowing with neurofilament condensation at Schmidt-Lanterman incisures with abnormal UML, suggesting axonal damage at those sites in the POEMS patient biopsies. Myelin sheath irregularity was conspicuous in large myelinated fibers and was associated with abnormally widened bizarrely shaped Schmidt-Lanterman incisures. Indirect immunofluorescent studies revealed abnormalities of sodium (pan sodium) and potassium (KCNQ2) channels, even at nonwidened nodes of Ranvier. Thus, UML was not apparently associated with segmental demyelination but seemed to be associated with axonal damage. These observations suggest that nodal ion channel disruption may be associated with functional deficits in POEMS syndrome patient nerves.
authors.affiliation: From the Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Rina
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Haruki
authors.initials: H
authors.lastname: Koike
authors.forename: Mie
authors.initials: M
authors.lastname: Takahashi
authors.forename: Ken
authors.initials: K
authors.lastname: Ohyama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kawagashira
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iijima
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D058967:Contactin 1 / Q000378:metabolism; D005260:Female; D006801:Humans; D051658:KCNQ2 Potassium Channel / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D016878:POEMS Syndrome / Q000473:pathology*; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D012867:Skin / Q000473:pathology; D013497:Sural Nerve / Q000473:pathology* / Q000648:ultrastructure
chemical_list: C548669:CNTN1 protein, human; D058967:Contactin 1; D051658:KCNQ2 Potassium Channel