| BackgroundSince 1970s,the role of autoantibody in neuromuscular disease has been recognized.Acetylcholine receptor antibody and voltage-gated calcium channel antibody both combine with protein of extracellular structural domain,and the pathogenesis has been verified in the vitro and vivo.Recently,with the development of autoantibody's researches,we have huge awareness of abnormal immune adjustment and autoimmune,and deepen the recognition in autoantibody and autoimmune encephalitis.Autoantibody encephalitis is a popular research in neurology at present.Limbic encephalitis(LE)mainly manifests as a decline in memory,ambiguity and epileptic seizures of acute and subacute onset.The middle temporal lobe shows high signal in magnetic resonance imaging(MRI)and cerebrospinal fluid(CSF)that suggests inflammatory change.In limbic encephalitis patients,voltage-gated potassium channel complex(VGKCs)antibody often can be found,but N-methyl-D-aspartate receptor(NMDAR)antibody,a-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor(AMPAR)antibody,?-aminobutyric acid receptor(GABAR)antibody and glycine receptor antibody rarely can be found.VGKCs are the potassium channels that regulate the excitability of neurons in the central nervous system and peripheral nervous system,which are composed of leucine-rich glioma inactivated 1 protein(LGI1)and contactin-associated protein-like 2(Caspr2).VGKCs antibodies were detected by radio-immuno-precipitation in mammalian brain tissue extracts.Besides,LGl1 antibody(+)is mostly common.LGI1 is a secreted protein that binds to the metalloproteinase family,mainly in the hippocampus and temporal cortex.It connects the presynaptic membrane metallopeptidase domain23(ADAM23)with the postsynaptic membrane metallopeptidase domain22(ADAM22),which plays an important role in the presynaptic membrane to the postsynaptic membrane AMPAR inhibitory signaling.LGI1 antibodies can reduce the interaction between LGI1-related metalloproteases,thereby reducing the accumulation of postsynaptic membrane AMPAR.Damaged human coding of the LGI1 protein gene can cause autosomal dominant inheritance of temporal lobe epilepsy.If mice are knocked out the LGI1 gene after three weeks of birth,they would die of fatal epilepsy.This confirms the LGI1's important role in the synaptic signal transmission.LGl1 antibody-positive limbic encephalitis(LGI1-LE)is rarely clinically significant,but with the progress of the study,the morbidity is also increasing.This disease mainly manifests subacute onset of memory disorders,epilepsy and mental disorders.Most of the normal cerebrospinal fluid in patients and oligoclonal band is rare,MRI can also be normal.But there are two characteristic clues that can help us to recognize the disease early,namely:faciobrachial dystonic seizures(FBDS)and hyponatremia.The disease is sensitive to immunotherapy,including hormones,immunoglobulin and plasma exchange,and the clinical prognosis is better.ObjectiveIn this study,we retrospectively analyzed the clinical data of 13 patients with limbic encephalitis enrolled with leucine-rich glioma inactivated 1 protein antibody,and discussed the clinical manifestations,clinical course and evolution,laboratory examination,video electroencephalogram(Video-EEG),imaging performance,treatment and prognosis,so as to improve the understanding of this disease.Method1.Object of study Choosing:13 patients in Qilu Hospital of Shandong University and Binzhou Medical University Hospital who were diagnosed leucine glioma inactivated 1 protein antibody-positive limbic encephalitis in 2015.03-2017.02.2.Retrospective analysis of clinical data:All the clinical manifestations,clinical course and evolution,laboratory examination,Video-EEG,brain MRI,treatment,prognosis and 6 months follow-up data were retrospectively analyzed.3.Determination of serum and cerebrospinal fluid LGI1 antibody:The titer of serum and cerebrospinal fluid LGI1 antibody was measured by titration plate technique.The procedure was strictly followed according to the instructions of the reagent.4.Statistical analysis:All statistical analyzes were performed by using statistical analysis software SPSS 23.0.The Fisher exact test was used to determine the statistical significance of the samples(P<0.05 was considered statistically significaant).Correlation analysis using the Spearman test,bilateral P values less than 0.01 were considered statistically significant.Result1.Clinical manifestationThe 13 patients,of which 11 were male,aged 43-72 years,with an average age of 62 ± 9.9 years.2 cases were female,aged 68-69 years old.Time from onset to diagnosis is 14 days to 7 months,of which 2 cases have infection recurrence.All patients showed epilepsy,9(69.2%)cases showed FBDS,2 cases showed loss in thought,5 patients had complete tonic clonic seizures,3 patients initially had FBDS,followed by the development of a comprehensive tonic clonic seizure;9(69.2%)patients had memory disorders;5(38.5%)cases of patients had psychiatric symptoms;2 patients showed movement disorders;2 patients showed sleep disorders.9(69.2%)patients had the first symptom of seizure,5(38.5%)patients had memory disorders,1(7.7%)patients had psychiatric symptoms.But with the progression of the disease,all patients had seizures,9 patients had memory disorders,5 patients had psychiatric symptoms,2 patients had movement disorders,and 2 patients had sleep disorders.Of the 9 patients with FBDS,4(44.4%)showed typical faciobrachial dystonic seizures,involving only the facial and upper limbs only.1 patient only manifested on the face;1 patient was affected on the upper limbs;2 patients involved side of the body,2 patients involved in one side of the face and one side of the limb.1 patient was attacked respectively on facial and upper limb.The frequency of attack is several times/day to more than 300 times/day.After antiepileptic drug treatment,in 4 patients:1 patient's frequency of onset decreased,2 patients had no change in frequency,1 patient is invalid and the frequency increased on the contrary.But the other 5 patients,who combined immunotherapy,the frequency of episodes decreased significantly,even completely disappeared(P = 0.01,statistically significant).2.Auxiliary examination8 patients' Brain MRI is normal.5 patients(38.5%)were abnormal,including:2 patients in the hippocampus,2 patients in the basal ganglia,1 patient in the corpus callosum area;1 patient of recurrent patients,whose Brain MRI prompted hippocampal atrophy.13 patients underwent lumbar puncture.2 patients of cerebrospinal fluid pressure was high.All patients had normal cerebrospinal fluid routine examinations.3 patients of cerebrospinal fluid protein increased,7(58.3%)patients of cerebrospinal fluid immunoglobulin IgG,IgA increased,immunoglobulin IgM were normal.All of the patients underwent Video-EEG.4patients showed sharp waves.4 patients were normal.5 patient presented diffuse slow waves or slow waves in frontotemporal areas.All patients took the checks of tumor markers,anti-nuclear antibodies,thyroid function,blood biochemical and rheumatoid series.1 patient had hypothyroidism;4 patients'carcinoembryonic antigen(CEA)slightly elevated,and abdominal ultrasound and computerized tomography(CT)examination were not found in the tumor.Of the 13 patients,9(69.2%)patients had vary degrees of hyponatremia and hypochloremia.With the treatment and the condition of relief,these laboratorial index can be restored to the normal range.All patients took serum and cerebrospinal fluid autoimmune antibody detection.All patients' serum LGI1 antibodies were positive,titer is between 1:10?1:100,and cerebrospinal fluid antibodies in 3 patients were negative,10 patients' were positive,titer is between 1.10?1:32.All patients' serum and cerebrospinal fluid NMDAR antibody,AMPAR antibody,Caspr2 antibody and GABAR antibody were negative.3.Cure and prognosisAll patients in this research were given antiepileptic drugs and immunotherapy.There was a positive correlation(r = 0.904,p = 0.000)between the starting time of immunotherapy and the recovery of the patient's symptoms to mRS(Modified Rankin Scale)= 1.The time to start use immunotherapy and/or antiepileptic drugs was positively correlated with the recovery of patient symptoms to mRS = 1(r = 0.881,p=0.000).In the period of follow up,7 patients remained seizures in the first three months,only 2 patients had seizures until the sixth month.ConclusionLGI1-LE is rarely clinically significant,so it is easy to misdiagnosis,and we should improve the understanding of the disease.LGI1 antibody-positive limbic encephalitis is common in male,and the average age of onset is 60 years old.It manifests acute or subacute onset with memory disorders,seizures and mental disorders,especially FBDS,hyponatremia,and it may be associated with sleep disorders,dyskinesia.Brain MRI shows in mesial temporal and hippocampus have abnormal signal.The blood and/or cerebrospinal fluid can be detected of LGII antibodies,cerebrospinal fluid IgG;IgA increased.It can be relapsed,and can be combined with other autoimmune diseases,rarely combined with the tumor.Once diagnosed,it should be given antiepileptic drugs,and immunotherapy treatments as soon as possible,in order to relieve patient symptoms,improve patient prognosis,and avoid hippocampal atrophy and refractory epilepsy. |
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