Right Under Our Noses: Olfactory Pathology in Central Nervous System Demyelinating Diseases
Objectives: To determine whether olfactory bulb and tract pathology is a feature of multiple sclerosis and other inflammatory demyelinating diseases.
Methods: A human autopsy cohort of pathologically confirmed cases encompassing the spectrum of demyelinating disease (multiple sclerosis (n=17), neuromyelitis optica (n=3), and acute disseminated encephalomyelitis (n=7)) was compared to neuroinflammatory (herpes simplex virus encephalitis; n=3), neurodegenerative (Alzheimer’s disease; n=3), and non-neurologic (n=8) controls. For each case, olfactory bulbs and/or tracts were stained for myelin, axons, and inflammation.
Results: Olfactory bulb/tract demyelination was frequent in all demyelinating diseases (multiple sclerosis 12/17 (70.6%); acute disseminated encephalomyelitis 3/7 (42.9%); neuromyelitis optica 2/3 (66.7%)) but was absent in herpes simplex encephalitis, Alzheimer’s disease, and non-neurologic controls. Inflammation was significantly greater in the demyelinating diseases compared to non-neurologic controls. Olfactory bulb/tract axonal loss was detected in all demyelinating diseases, being most severe in multiple sclerosis 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 and inflammation mirrored that found in superficial cortical layers where subpial demyelination and inflammation was observed.
Conclusions: We provide unequivocal evidence that olfactory bulb/tract demyelination is frequent, can occur early, is highly inflammatory and specific to demyelinating disease. These novel findings shed insight into the pathogenesis of demyelinating diseases and fuel support for further exploration of the nose to brain hypothesis.