The recently described disease with antibodies against IgLON5 (immunoglobulin-like cell adhesion molecule 5), is characterized by a distinctive sleep disorder associated with a broad variety of neurological symptoms such as gait instability, movement disorders, and brainstem involvement. IgLON5 is an adhesion molecule widely expressed in the CNS, but whose precise function is poorly understood. The disease differs from other types of autoimmune encephalitis in that its symptoms are different and the development of the disease is thought to be slower. In addition, abnormal proteins are deposited in the affected brain regions, similar to those seen in certain dementia diseases. Anti-IgLON5 disease is a rare disease, with an estimated incidence of 1/150,000.
Anti-IgLON5 disease affects men and women equally. In currently documented cases, the median age at diagnosis was 62 years, ranging from 45 to 79 years.
The most prominent feature of the anti-IgLON5 disease is a distinctive sleep disorder, including both REM and non-REM parasomnia, finalistic movements and sleep disordered breathing with stridor and Obstructive Sleep Apnea. In the review published by Nissen and Blaabjerg (2019), they found that sleep disorder was present in 83% of patients and as part of initial symptoms in 40%. Gait instability, difficulty swallowing, and movement disorders were found in > 60% of patients. Neuropsychiatric symptoms were found in 50% (cognitive impairment, memory deficits, and hallucinations), dysautonomia in 41% (urinary incontinence or urgency, constipation), dysarthria (present in 38% of cases), and symptoms of the peripheral nervous system in 32% (fasciculations, cramps, neuropathy).
Antibodies to IgLON5 can be found in both serum and CSF and are positive in 95 and 100% of patients. Antibody testing is most crucial in diagnosing this disease and it is recommended to test both serum and CSF. Other CSF findings include elevated protein level, seen in 49% of cases, and pleocytosis, found in 24% of cases. Brain MRI and EEG are normal in the majority of cases. Brain FDG-PET CT is abnormal in 50% of cases, and could be more sensitive than MRI.
Anti-IgLON5 disease can be readily suspected if one considers the combination of a distinctive sleep disorder in association with one or more of the following symptoms: bulbar dysfunction, gait difficulties, oculomotor abnormalities, chorea, or cognitive deterioration.
A tumor is rarely seen, but when found it is often a thymoma.
Anti-IgLON5 disease is treated with first-line therapy (corticosteroids and IVIG/ plasmapheresis). In case of ineffectiveness can be treated with Rituximab or cyclophosphamide.
Many patients will need breathing supportive treatment at night or throughout the day.
Aggressive immunotherapy seems to be crucial for outcome, as untreated patients or patients treated with steroid monotherapy appear to have a higher mortality.
Morten Blaabjerg, MD, PhD, Odense University Hospital, Department of Neurology, Odense, Denmark