[Anti-IgLON5 syndrome - what is our current understanding?]

In 2014, antibodies against the cell surface protein IgLON5 were first described in patients with a complex neurological syndrome of sleep disturbances and movement disorders. Since then, the clinical spectrum has steadily expanded and now includes brainstem syndromes, autonomic and neuropsychiatric disorders and, more rarely, peripheral symptoms such as fasciculations and neuromyotonia. Anti-IgLON5 antibodies are thought to cause neurodegeneration in specific CNS regions with tau deposits ("tauopathy"). There is a clear association with the HLA alleles DQB1*05:01 and DRB1*10:01. Anti-IgLON5 antibodies have been identified with a prevalence of 12 in 150,000 patients per year, but the estimated number of unreported patients might be much higher. Current therapeutic options include immunomodulation and immunosuppression; however, the clinical response remains poor and the mortality continues to be high. The unsatisfactory response seems to be related to a pathogenic mechanism that is still enigmatic, and as well to the delayed start of treatment in most cases. This review summarizes the current opinion on the pathogenic mechanism, clinical presentation and recommendations for diagnostics and therapy.