Clinical Analysis Of 30 Patients With Leucine-rich Glioma Inactivated-1 Protein Antibody-mediated Encephalitis

Background and objectiveAutoimmune encephalitis refers to a group of inflammatory brain diseases that manifests with prominent neuropsychiatric symptoms and is associated with antibodies against neuronal cell surface proteins,ion channels or receptors.According to different anti-neuron antibodies and clinical syndrome classification,one of the most frequent types of autoimmune encephalitis predominantly affects the limbic system(limbic encephalitis)and can result from autoantibodies against different antigens,such as leucine-rich glioma-inactivated 1 protein(LGI1),the y-aminobutyric acid type B receptor(GABABR),or contactin-associated protein-like 2(CASPR2).The most frequent is autoimmune limbic encephalitis with antibodies against LGI1.Anti-LGI1 encephalitis is mediated by LGI1 antibodies and associated with proteins on the cell membrane surface of neurons.At present,its exact pathogenic mechanism is not clear,and clinical studies with large samples are still rare,so it is still the focus of clinical research.Recent epidemiological studies have shown that the incidence of anti-LGI1 antibody-associated encephalitis is on the rise.With the expansion of neurons antibodies spectrum and a lot of research,LGI1 antibody-associated encephalitis can be combined with multiple anti-neuron antibody positive or other autoimmune diseases,resulting in an increase in clinical phenotype and complex symptoms.The diagnosis mainly depends on the examination of antibodies in serum or cerebrospinal fluid,which may lead to misdiagnosis and delayed treatment.So,it is challenging to distinguish autoimmune encephalitis from the clinical perspective.This study was to analyzed the clinical data of 30 patients with anti-LGI1 encephalitis and summarized their clinical characteristics combined with the latest relevant literature,so as to improve a further understanding on this disease and do help to early diagnosis and prognosis evaluation.Materials and methodsIn this study,the clinical data of 30 patients with anti-LGI1 encephalitis diagnosed in the First Affiliated Hospital of Zhengzhou University were collected from November 2017 to October 2019.The clinical characteristics were retrospectively analyzed,including gender and age distribution,prodromal symptoms,first symptoms,main clinical manifestations,related auxiliary examination,treatment measures and prognosis.Using the modified Rankin score scale(mRS)to evaluate the effect before and after treatment,outpatient service or telephone follow-up was conducted to analyze the outcome and prognosis.Results1.Among 30 patients,there were 24 males and 6 females,male:female=4:1 age from 15 to 82 years old.The median age was 61 years old and the peak incidence was 50 to 70 years old.The interval from the first onset to the diagnosis ranged from 5 days to half a year,with a median interval of 30 days and an average interval of 37 days.2.Among 30 patients,5 cases(17%)had clear inducement before onset,including 3 cases of fatigue,1 case of upper respiratory tract infection and 1 case of herpesvirus infection.3 patients(10%)had non-characteristic prodromal symptoms,such as dizziness,limb weakness,and paroxysmal chest distress.3.Among 30 patients,the initial symptoms of 21 patients(70%)were the limbic encephalitis symptoms,including 11 patients(37%)with onset of seizures,7 patients(23%)with cognitive dysfunction and 3 patients(10%)with mental and behavior disorder.5 patients(17%)had facial-brachial dystonia as the first symptom.There were 3 patients(10%)started with paroxysmal limb numbness and weakness and 1 patient(3%)with dizziness.4.During the total course of the disease,the main clinical symptoms include cognitive dysfunction(73%),seizures(47%),sleep disorders(43%),facial-brachial dystonia(33%),autonomic dysfunction(30%),mental and behavioral disorder(27%),involuntary movement(17%)and disturbance of consciousness(13%).5.Among 30 patients,12 patients(40%)had hyponatremia.24 patients were tested for thyroid function and antibodies,in which 3 patients(13%)of thyroid antibodies were abnormal.22 patients were tested for connective tissue related antibodies,and 2 patients(9%)were abnormal.8 patients were tested for serum tumor markers,4(22%)of them were abnormal.6.Among 30 patients,27 patients underwent lumbar puncture examination.The range of intracranial pressure was 60 to 245mmH2O.Intracranial pressure increased in 2 cases(7%)and decreased in 1 case(4%).White blood cell count increased in 3 cases(11%),lymphocyte proportion increased in 8 cases(30%),and protein concentration increased in 9 cases(33%).The routine examination of cerebrospinal fluid were non-specific changes.7.Among 30 patients,15 cases were tested for cerebrospinal fluid and serum antibodies in the same period,of which 12 cases(80%)were positive for LGI1 antibody in cerebrospinal fluid and 15 cases(100%)were positive for LGI1 antibody in serum.Multiple anti-neuronal antibodies were positive in 2 cases(7%),of which 1 case was positive for anti-NMDAR antibody and 1 case was positive for anti-Hu antibody.8.Among 30 patients,8 patients(27%)had abnormal cranial MRI,involving the frontal lobe,parietal lobe,temporal lobe,hippocampus and basal ganglia.EEG examination was performed in 23 patients,of which 3 patients(13%)were abnormal,mainly manifested as non-specific diffuse slow wave.9.All the patients in this group were treated with immunotherapy,and glucocorticoid was widely used(57%).After immunotherapy,the condition of the patients was improved to some extent,3 patients(10%)relapsed during the follow-up.Conclusion1.Anti-LGI1 antibody encephalitis was more common in middle-aged and elderly men,and the peak incidence is 50 to 70 years old.The main manifestation is the clinical symptoms of limbic encephalitis,including mental and behavior abnormalities,cognitive impairment and seizures.Facial-brachial dystonia,hyponatremia,sleep disorders,autonomic nervous dysfunction and involuntary movement also occur in anti-LGI1 antibody encephalitis.Non-specific symptoms such as arrhythmia and paroxysmal chest discomfort need clinical attention.2.The positive rate of LGI1 antibody in serum was higher than that in cerebrospinal fluid with indirect immunofluorescence in the same period.3.Anti-LGI1 antibody encephalitis can be combined with multiple anti-neuron antibody,which can affect the clinical manifestations of patients and results in variation and overlap of them.4.Cranial MRI abnormalities in anti-LGI1 antibody encephalitis were mainly manifested in temporal lobe,hippocampus and basal ganglia.In patients with FBDS,abnormal signal in the basal ganglia may be an important sign.5.Tumor was uncommon in Anti-LGI1 antibody encephalitis.Immunotherapy is effective,some patients can be completely return to normal.The remaining symptoms were mainly memory loss.