Anti-Iglon5 Syndrome: What We Know So Far? A Non-Systematic Review

Abstract

The objective of this review is to provide an overview of the current knowledge of Anti-IgLON5 syndrome. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 is crucial for the Anti-IgLON5 Syndrome diagnosis. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent, and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at the hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata, and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. Early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The Anti-IgLON5 syndrome mortality is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends on some clinical and analytical characteristics. In addition, future studies are needed to thoroughly analyze the aspects of pathogenesis and treatment of this important pathological syndrome.

Anti-IgLON5 Disease – The Current State of Knowledge and Further Perspectives

“…Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), could indicate that anti-IgLON5 is a novel tauopathy ( 17 ). Neuropathological investigations have shown that hyperphosphorylated tau has a propensity to gather in structures located in the basal part of the brain, including the hypothalamus, the tegmentum and periaqueductal gray matter ( 5 ). The correlation between the amount of aggregates and symptom severity needs to be investigated further.…”

“…IgLON genes can also regulate the level of renal perfusion due to glomerular afferent and efferent innervation and IgG anti-IgLON5 reactivity against renal glomeruli ( 3 , 4 ). The molecular structure of the IgLON5 protein can induce the production of specific antibodies in some cases, whose presence is crucial for anti-IgLON5 disease diagnosis, occurring with nonspecific symptoms like breathlessness during sleep, cognitive deterioration, gait disturbance and dysregulation of autonomic central nervous system (CNS) activity ( 5 ). The first cases of patients presenting i.a.…”

“…It has not been fully established whether intense inflammatory response mediated by antibody activity leads to neurodegeneration or if the ongoing tau pathological accumulation exacerbates the immunological response ( 5 ). Therefore, the exact nature of the disease remains unclear.…”

“…Prevalence of anti-IgLON5 antibodies is estimated at 12 out of 150 000 patients per year, although it is believed to be higher due to numerous cases being incorrectly diagnosed and reported ( 5 , 12 ). Most commonly, diagnosis is made among elderly patients, with no sex predominance, although the disease onset is designing and may occur between the ages of 45 and 70 ( 5 , 13 ). The literature points out that anti-IgLON5 antibodies found in serum or CSF are the necessary element of a definite diagnosis ( 11 ).…”