Anti-IgLON5 disease

Carles Gaig MD PhD (

Dr. Gaig of Hospital Clínic of Barcelona has no relevant financial relationships to disclose.

)
Francesc Graus MD PhD, editor. (Dr. Graus of the University of Barcelona has no relevant financial relationships to disclose.)
Originally released September 16, 2019; expires September 16, 2022

This article includes discussion of anti-IgLON5 disease, anti-IgLON5 syndrome, IgLON5 disease, IgLON5 encephalopathy, anti-IgLON5–related tauopathy, anti-IgLON5 sleep disorder, and IgLON5-associated encephalitis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Anti-IgLON5 disease is a newly identified neurologic disorder associated with antibodies in serum and CSF against IgLON5, a neuronal surface protein of unknown function. The disease is characterized by a distinctive sleep disorder associated with symptoms of brainstem dysfunction, gait instability, and a variety of other neurologic symptoms (eg, chorea, cognitive impairment). Anti-IgLON5 disease is associated with specific HLA haplotypes, but neuropathological examinations show a novel neuronal tauopathy predominantly involving the tegmentum of the brainstem and hypothalamus. At present, the exact pathogenesis is unclear, but these findings put anti-IgLON5 disease at the confluence of neurodegenerative and autoimmune mechanisms.

Key points

 

• Patients with anti-IgLON5 disease usually present a distinctive sleep disorder characterized by a NREM and REM parasomnia associated with stridor and obstructive sleep apnea.

 

• Neurologic symptoms beyond sleep are often the presenting symptom leading to medical consultation and may overshadow the sleep disorder.

 

• In addition to sleep problems, symptoms of bulbar dysfunction and gait abnormalities are frequent at disease presentation.

 

• Other symptoms are movement disorders, including chorea and abnormal cranial movements (eg, facials spams, myokymia, or myorhythmia), oculomotor abnormalities, cognitive impairment, and symptoms of nervous system hyperexcitability (eg, stiffness, spasms, cramps, or fasciculations).

 

• All of these symptoms result in different clinical subtypes at presentation, including (1) the sleep disorder; (2) a bulbar syndrome; (3) gait instability with supranuclear gaze palsy (or PSP-like subtype); (4) cognitive impairment, sometimes with chorea (mimicking Huntington disease); (5) isolated gait ataxia; and (6) a stiff-person–like syndrome.

Historical note and terminology

Anti-IgLON5 disease was described in 2014 in 8 patients presenting a neurologic syndrome with a prominent sleep disorder and antibodies directed to a neuronal surface protein named IgLON5 (Sabater et al 2014). Neuropathology in 2 patients showed neuronal loss and deposits of hyperphosphorylated tau protein in the brainstem tegmentum and hypothalamus. Since then, more than 70 cases have been reported, and the spectrum of neurologic symptoms and presentations is expanding (Gaig and Compta 2019). The underlying pathophysiology is still unclear, but the current evidence places the disease in interplay between autoimmunity and neurodegeneration.

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