title: Olfactory Pathology in Central Nervous System Demyelinating Diseases.
abstract: Olfactory dysfunction is common in multiple sclerosis (MS). Olfactory bulb and tract pathology in MS and other demyelinating diseases remain unexplored. A human autopsy cohort of pathologically confirmed cases encompassing the spectrum of demyelinating disease (MS; n = 17), neuromyelitis optica [(NMO); n = 3] and acute disseminated encephalomyelitis [(ADEM); n = 7] was compared to neuroinflammatory [herpes simplex virus encephalitis (HSE); n = 3], neurodegenerative [Alzheimer's disease (AD); n = 4] and non-neurologic (n = 8) controls. For each case, olfactory bulbs and/or tracts were stained for myelin, axons and inflammation. Inferior frontal cortex and hippocampus were stained for myelin in a subset of MS and ADEM cases. Olfactory bulb/tract demyelination was frequent in all demyelinating diseases [MS 12/17 (70.6%); ADEM 3/7 (42.9%); NMO 2/3 (66.7%)] but was absent in HSE, AD and non-neurologic controls. Inflammation was greater in the demyelinating diseases compared to non-neurologic controls. Olfactory bulb/tract axonal loss was most severe in MS where it correlated significantly with the extent of demyelination (r = 0.610, P = 0.009) and parenchymal inflammation (r = 0.681, P = 0.003). The extent of olfactory bulb/tract demyelination correlated with that found in the adjacent inferior frontal cortex but not hippocampus. We provide unequivocal evidence that olfactory bulb/tract demyelination is frequent, can occur early and is highly inflammatory, and is specific to demyelinating disease.
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Gabriele C
authors.initials: GC
authors.lastname: DeLuca
authors.affiliation: Oxford Medical School, University of Oxford, Oxford, UK.
authors.forename: Albert
authors.initials: A
authors.lastname: Joseph
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Jithin
authors.initials: J
authors.lastname: George
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Yates
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Hamard
authors.affiliation: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, UK.
authors.forename: Monika
authors.initials: M
authors.lastname: Hofer
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Esiri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002648:Child; D003711:Demyelinating Diseases / Q000473:pathology*; D004660:Encephalitis / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000473:pathology; D009830:Olfactory Bulb / Q000473:pathology*; D055815:Young Adult
keywords: demyelinating disease; multiple sclerosis; neuroinflammation; olfaction; pathology