Objective:

Background:

Anti-IgLON5 disease sits at the crossroads between autoimmunity and neurodegeneration. The presence of the Anti-IgLON5 antibody, along with an association with certain HLA subtypes, suggests an autoimmune pathology. The deposition of hyperphosphorylated tau within the brainstem, tegmentum, hypothalamus, and hippocampus indicates a neurodegenerative process. This explains the disease’s multifarious presentation, often mimicking other entities and causing diagnostic delays. It may present with REM or Non-REM sleep disorders similar to Morvan’s syndrome, dysautonomia like in Multiple system atrophy or autonomic failures, various bulbar symptoms of brainstem syndromes, neuromuscular manifestations such as in Myasthenia gravis or motor neuron disease, cognitive impairment as in Alzheimer’s dementia, movement disorder as in Stiff person syndrome or Huntington’s disease and oculomotor abnormalities as in progressive supranuclear palsy.  

Design/Methods:

Retrospective chart review of a patient who presented to the University of Kentucky

Results:

A 59-year-old male with a year long history of insomnia, dream enactment behavior, oneiric stupor, behavioral changes, gait impairment, unintentional severe weight loss, itching sensation over the abdomen and orthostatic hypotension. Polysomnography revealed a complete inability to sleep. MRI head showed mild global atrophy along with non-specific white matter changes. On examination, he was alert but fidgety with pressured speech, with truncal ataxia, dysmetria, lower extremity proprioceptive loss, limb myoclonus with rare fasciculations. Despite the broad differential diagnosis, the high pre-test probability was confirmed with an elevated serum titer of anti-IgLON5 antibody at 1:960. CSF studies revealed a cell count of 5, mildly elevated protein at 57, elevated IgG index, normal myelin basic protein, 7 oligoclonal bands, along with elevated CSF tau levels. 

Conclusions:

IgLON5 disease is a rare and fascinating illness, and should be considered in patients who present in the appropriate clinical context: with an unexplained sleep disorder, bulbar symptoms, movement disorders, dysautonomia or CNS hyperexcitability.