Autoimmune encephalitis with antibodies against Leucinie-rich Glioma Inactivated 1 and γ-aminobutyric acid-beta-receptor: case report and literature review

A 60-year-old man presented with slow response and psychosis. Apart from hyponatremia, serum test also showed positive anti-Leucinie-rich Glioma Inactivated 1 (anti-LGI1) and anti-γ-aminobutyric acid-beta-receptor (anti-GABA B R), and electroencephalogram exhibited moderate diffusion abnormality. The patient responded well to steroid treatment. Here we report the rst autoimmune encephalitis(AE) characterized by positive anti-LGI1 and anti-GABA B R, as well as summarizing AE with multiple auto-antibodies reported so far, hopefully to provide experience for clinical practice.


Background
There are basically two kinds of auto-antibodies related to autoimmune encephalitis(AE). One is against neuron surface receptor, among which anti-N-methyl-D-aspartic acid receptor (anti-NMDAR) is the most common, others also including anti-γ-aminobutyric acid-beta-receptor (anti-GABA B R), anti-α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid receptor (anti-AMPAR), anti-Leucinie-rich Glioma Inactivated 1 (anti-LGI1), etc. The other kind is against neuronal intracellular antigen, mainly referring to classic paraneoplastic neurosis antibody, such as anti-Hu, etc [1][2] . Different types of auto-antibodies correspond to speci c neurological syndrome, which has strong speci city or directivity for etiological diagnosis. The majority of AE patients have only one of the above auto-antibodies, and very few with multiple autoantibodies. Herein we report a patient with positive anti-LGI1 and anti-GABA B R who improved greatly by steroid therapy.

Case Presentation
A 60-year-old Chinese male presented with one-month of slow response and abnormal behavior. He had typhia 40 years ago and left no sequel. Neurological exam revealed poor mental state, slow response and damaged memory, attention, calculation and orientation.
Mini mental state examination score was 15. Cerebrospinal uid (CSF) electrophoresis IgG index was 0.71 (reference 0.3~0.7). Intracranial pressure was 150mmH 2 O. CSF routine biochemistry for protein content and glucose were normal and infectious test for virus, tuberculosis and Cryptococcus were negative. CSF cytology and cytometry were negative for malignant cells. Brain MRI scan with contrast enhancement was normal. Chest enhanced CT scan revealed in ammation in left lower lobe. Serum procalcitonin was 0.048ng/mL (reference<0.046ng/mL), C reaction protein was 8.05mg/L (reference<5mg/L). Serum AE antibody spectrum demonstrated positive anti-LGI1 IgG and anti-GABA B R IgG, while CSF auto-antibody test was negative. Blood studies revealed sodium was 119mmol/L (reference 135~153mmol/mL) and chlorine was 81mmol/L (reference 90~110mmol/L) at rst admission. Electroencephalogram (EEG) indicated moderate diffusion abnormality ( Figure 1A and 1B).
For treatment of AE with multiple co-existing antibody, he received 1g and 0.5g intravenous methylprednisolone separately, 3 days for each dosage, and then remained on an oral steroid taper for half year. After intravenous and oral sodium supplement, blood sodium and chlorine gradually increased to normal (Table 1). His mental state improved greatly and EEG recovered to normal.  year-old patient, with subacute onset, mainly manifested cognitive decline, behavioral abnormality and hyponatremia. The serum anti-LGI1 and anti-GABA B R were double positive, and EEG indicated moderate diffusion abnormality. According to the patients' symptoms, AE auto-antibody spectrum test and EEG results, the patient was diagnosed as AE with double auto-antibody positive, ie, anti-LGI1 and anti-GABA B R. The patient responded well to glucocorticoid treatment, and we will continue to follow up the prognosis.
Anti-LGI1 encephalitis, which is mostly found in elderly men with subacute onset, is related to  [3][4] . Anti-GABA B R encephalitis mostly presents limbic encephalitis symptoms, with temporal lobe epilepsy as the core symptomatology, and most of them are accompanied by cognitive function decline, personality change and mental behavior abnormality. About 50% of patients have small cell lung cancer or neuroendocrine tumor. It is suggested that anti-GABA B R encephalitis should further take chest CT or PET examination [5] .
The overlying of neuronal auto-antibodies may cause the superposition of clinical syndrome, but not a simple complete superposition, which needs to be analyzed according to the speci c antibody type and clinical manifestation. According to Professor Guan Hongzhi's newly published review, it is necessary to distinguish whether the antibodies in patients belong to pathogenic markers or concomitant antibodies [6] .
The main manifestations of this case are psychobehavioral abnormality and hyponatremia, more similar to clinical manifestations of anti-LGI1 AE.
Qi Hengchang reported two cases of AE with multiple auto-antibodies against neuron (one was anti-NMDAR(+), anti-GABA B R(+), and the other anti-LGI1(+), anti CASPR2(+). Both patients were adult women with acute onset. Their rst symptom was epilepsy, and the treatment effect was good [10] .
The clinical signi cance of multiple auto-antibody has already raised attention of many neurologists and needs to be interpreted in combination with clinical practice. For example, anti-GABA B R can be combined with anti-Hu. When anti-GABA B R is positive, it is recommended to screen anti-Hu and carry out tumor screening at the same time, such as chest CT, tumor markers, etc., excluding the possibility of tumor as much as possible. In this case chest enhanced CT scan didn't nd tumor, but the patient was advised to take regular examination during follow-up. At present, many reports of anti-NMDAR combined with anti-MOG suggest that it is necessary to consider the clinical syndrome superposition caused by the antibody superposition, pay attention to the clinical process, and inquire in detail the history and imaging data whether there is a basis for demyelination [11] .

Consent for publication
Written informed consent was obtained from the patient for publication of this case report and companying images.

Availability of data and materials
All data generated or analyzed during this study are included in this published article.

Competing Interests
The authors declare that they have no competing interests.

Acknowledgements
Not applicable.

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