18
AASM Membership Sections Newsletter
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Issue #7
reviewed specifically looking for sleep disorders as well as the
associate symptoms, confirming that all had a sleep breathing
disorder plus abnormal sleep behaviors. At that time the
antigen had been identified by the neuroimmunology team:
the target antigen of all patients’ antibodies was IgLON5,
the latest identified member of the IgLON family, which is
part of the immunoglobulin superfamily of cell adhesion
molecules. The family of IgLON proteins has important
functions in neuronal pathfinding and synaptic formation
during brain development but there was no information of a
pathological relevance in humans. Standard treatment with
immunotherapy was tried in our four patients but there were
no consistent improvement on patients’ symptoms. During
the ensuing months the female patient and one of the males
died unexpectedly during their sleep and their brains could be
examined by Dr. Ellen Gelpi at the Brain Bank of our research
institute (IDIBAPS). Surprisingly, instead of inflammatory
changes she found neuronal loss and tau protein deposits
mainly in the brainstem tegmentum and hypothalamus,
a pattern more suggestive of neurodegeneration than of
autoimmune damage. The thalamus was preserved as well as
the cortex. Our findings suggested an intriguing link between
IgLON5 antibodies and a neuronal loss and tauopathy.
Whether IgLON5 antibodies are a primary or secondary event
in the pathophysiology of the disorder is unclear and further
research is needed.
The description of this novel disorder, the Iglon5 parasomnia,
is the result of a collaborative effort: neither of the
teams involved in this work –sleep, neuroimmunology or
neuropathology- could by themselves have performed the
entire task, no matter how good they could be in their field.
