Anti-IgLON5 Disease with intriguing MRI findings respond dramatically to immunotherapy

Background We present the first case of Anti-IgLON5 disease with unremarkable or unspecific brain magnetic resonance imagings, and poor responsiveness to immunotherapy. Case presentation A 37-year-old man presented with 4-day history of gait instability, dysarthria, and oculomotor abnormalities. The initial neurologic examination revealed mild unsteady gait, subtle dysarthria, and left abducent paralysis. The brain MRI imaging showed multiple, scattered diffusion restriction in the bilateral cerebral hemispheres involving left tegmentum of the midbrain, and occipital horn of right lateral ventricle, without contrast enhancement. The Anti-IgLON5 antibodies were detected in the serum (titer 1:32). Furthermore, the human leukocyte antigen (HLA) genotyping confirmed HLA-DRB1*11:01 and HLA-DRB1*15:01, HLA-DQB1*03:01 and HLA-DQB1*06:02 alleles. The symptoms of patient rapid improvement after high-dose intravenous methylprednisolone and immunoglobulins. Conclusions In this paper, we report a new case of anti-IgLON5 disease with major symptoms of gait instability, dysarthria, and oculomotor abnormalities, with distinctive brain magnetic resonance findings, and responsive to immunotherapy. Yan Pi: report concept and design and drafting of the manuscript. Jingcheng Li and Kai Chang: report concept and design and editing of the manuscript for critical intellectual content. Lili Zhang: acquisition of data, interpretation of data, critical revision of final manuscript for intellectual content.


Abstract
Background We present the first case of Anti-IgLON5 disease with unremarkable or unspecific brain magnetic resonance imagings, and poor responsiveness to immunotherapy.
Case presentation A 37-year-old man presented with 4-day history of gait instability, dysarthria, and oculomotor abnormalities. The initial neurologic examination revealed mild unsteady gait, subtle dysarthria, and left abducent paralysis. The brain MRI imaging showed multiple, scattered diffusion restriction in the bilateral cerebral hemispheres involving left tegmentum of the midbrain, and occipital horn of right lateral ventricle, without contrast enhancement. The Anti-IgLON5 antibodies were detected in the serum (titer 1:32). Furthermore, the human leukocyte antigen (HLA) genotyping confirmed HLA-DRB1*11:01 and HLA-DRB1*15:01, HLA-DQB1*03:01 and HLA-DQB1*06:02 alleles. The symptoms of patient rapid improvement after high-dose intravenous methylprednisolone and immunoglobulins.
Conclusions In this paper, we report a new case of anti-IgLON5 disease with major symptoms of gait instability, dysarthria, and oculomotor abnormalities, with distinctive brain magnetic resonance findings, and responsive to immunotherapy.

Background
Anti-IgLON5 disease was first described as a progressive antibody-associated encephalopathy, with multiple non-specific clinical symptoms including sleep dysfunction, bulbar symptoms, progressive supranuclear palsy-like syndrome, cognitive impairment, and a variety of movement disorders. This newly discovered disease presented unremarkable or unspecific brain magnetic resonance imagings, and had poor responsiveness to immunotherapy.

Case presentation
A 37-year-old man presented with 4-day history of gait instability, dysarthria, and oculomotor abnormalities. He did not report parasomnia (only excessive daytime sleepiness), there was no family history either. The initial neurologic examination revealed mild unsteady gait, subtle dysarthria, and left abducent paralysis. In addition, although the patient was able to walk alone, he felt unsteady with a subjective feeling of lateropulsion. The rest of his examination was normal. and did not show the same HLA association found in other reported cases [1][2][3][4].
Finally, the EGG and PSG findings were unremarkable.
The patient was initially treated with high-dose intravenous methylprednisolone and immunoglobulins, which led to a rapid improvement over a few days. When discharged, his gait instability, dysarthria, and oculomotor abnormalities completely recovered. The titer of serum anti-IgLON5 antibodies decreased to 1:10 atfer this treatment, and the initial MRI changes have lessened. The patient continued treatment with mycophenolate mofetil, and oral steroids were tapered slowly over several months.

Discussion and conclusions
Anti-IgLON5 disease was first described in 2014 as a progressive antibodyassociated encephalopathy by Sabater L et al. [4]. The main symptoms are heterogeneous, including sleep dysfunction, bulbar symptoms, progressive supranuclear palsy-like syndrome, cognitive impairment, and a variety of movement disorders [5]. These symptoms may each occur in different severity, combinations and periods, leading to various clinical subtypes. Reportedly, more than 95% cases presented unremarkable or unspecific MRI findings [5], and had poor responsiveness to immunotherapy. In contrast, our case showed distinctive brain MRI changes, particularly in left tegmentum of the midbrain, and occipital horn of right lateral ventricle, which haven't been reported before. After the treatment of corticosteroids and immunoglobulins, his symptoms improved dramatically, his anti-IgLON5 serum titer decreased from 1:32 to 1:10, and his initial brain MRI changes have lessened, all this suggests that his symptoms could be associated with the titer of anti-IgLON5 antibodies and the antibodies may play a crucial role in the pathogenesis.
Additionally, the positive treatment response to immunotherapy in this patient might also be related to the young age of onset (37 years old) and the only short duration (4 days), while the youngest patient reported in the literature was 40 years old [1] and the shortest duration was 3 months [6]. In this scenario, an early diagnosis and treatment would be crucial to delay or even stop the progress of the