Anti-IgLON5 Disease: A Case With 11-Year Clinical Course and Review of the Literature

Abstract

Background: Anti-IgLON5 disease is a novel disorder with a complex interplay between inflammation and neurodegeneration. Patients develop antibodies against IgLON5 but also deposition of neuronal tau protein. Symptoms often have an insidious onset, slow progression and mimic other neurological disorders. Here we report a case with severely prolonged 11-year disease course and provide a review of current reported cases with focus on presentation, work-up, treatment, and outcome.Method: All reported cases of anti-IgLON5 disease were evaluated. Cases reported twice (in case series and as single case reports), were carefully excluded.Results: Most patients display a characteristic sleep disorder with severe insomnia, non rapid eye movement (NREM) parasomnia, with finalistic movements and sleep disordered breathing (stridor and obstructive sleep apnea). Other symptoms are bulbar involvement, gait instability, movement disorders, oculomotor abnormalities, dysautonomia, and peripheral symptoms. Antibodies are present in both serum and CSF and there is a strong correlation with human leukocyte antigen (HLA) DRB1*10:01 and HLA-DQB1*05:01. Neuropathological examination reveals neurodegeneration with neuronal tau deposits in regions that correlate with the clinical presentation (e.g., predominantly hypothalamus and tegmentum of the brain stem). Majority of cases respond partially to immunotherapy. Cases, who received no treatment or treatment with IV corticosteroids alone, had a higher mortality than cases treated with more potent immunotherapy.Conclusion: The clinical spectrum of Anti-IgLON5 disease continues to expand. Further studies are needed to elucidate the pathophysiology, therapeutic strategies and outcome in this novel disorder. Aggressive immunotherapy seems to increase survival.

Investigation of anti-IgLON5-induced neurodegenerative changes in human neurons

“…Anti-IgLON5 disease is rare with an estimated incidence of 1/150 000 with only 2 cases documented in Denmark (Nissen and Blaabjerg 2019). One patient has died and we were limited to use serum samples from only one single patient.…”

“…It was initially recognized as a sleep disorder with non-rapid eye movement (NREM) and REM parasomnia, breathing dysfunction, gait instability and bulbar symptoms, with serum and cerebrospinal fluid (CSF) antibodies against a neuronal adhesion molecule, named IgLON5 (Sabater et al 2014). The disease is now known to be more clinically heterogeneous in regards to presenting symptomatology and in its response to immunotherapy (Gaig et al 2017; Nissen and Blaabjerg 2019). The disease onset is insidious, progressing slowly over several years and has a fatal outcome if left untreated (Gaig et al 2017).…”

“…REM behavior disorder (RBD) and sleep-breathing difficulties such as obstructive sleep apnea (OSA) and stridor, can present early but also late in the course of disease (Gaig et al 2018). Brain imaging usually shows normal or nonspecific findings on cerebral magnetic resonance imaging (MRI) with patterns of brainstem/cerebellar atrophy or hyperintensities in regions most affected by phosphorylated Tau (p-Tau) deposition (hypothalamus, brainstem, hippocampus, cerebellum) (Nissen and Blaabjerg 2019; Gaig and Compta 2019). CSF analysis can show normal to mildly increased protein levels and slight pleocytosis in the range of 5 – 10 leukocytes/ μL (Nissen and Blaabjerg 2019).…”

“…Brain imaging usually shows normal or nonspecific findings on cerebral magnetic resonance imaging (MRI) with patterns of brainstem/cerebellar atrophy or hyperintensities in regions most affected by phosphorylated Tau (p-Tau) deposition (hypothalamus, brainstem, hippocampus, cerebellum) (Nissen and Blaabjerg 2019; Gaig and Compta 2019). CSF analysis can show normal to mildly increased protein levels and slight pleocytosis in the range of 5 – 10 leukocytes/ μL (Nissen and Blaabjerg 2019). More commonly, low to moderate intrathecal protein elevation presents without pleocytosis or oligoclonal bands (OCB) (Blinder and Lewerenz 2019).…”

Tauopathy and Movement Disorders—Unveiling the Chameleons and Mimics

“…Subsequently, many other phenotypes (chameleons) have emerged and most of the times they overlap ( 51 , 134 – 137 ) ( Table 4 ). MRI brain is mostly normal or may show cerebellar, brainstem atrophy ( 138 ). Recognition of these clinical phenotypes of anti IgLON5 are necessary because of its treatability with immunomodulators can prevent further neurodegeneration.…”