The Clinical Analysis Of Anti-Contactin Associated Protein-Like 2 Antibody Related Encephalitis

BackgroundAutoimmune encephalitis(AE)is a kind of encephalitis caused by the reaction of the autoimmune system to antigens of the central nervous system.It has become one of the research hotspots in the field of neuroimmunology in recent years.With an acute or sub-acute onset,the main manifestations of patients with AE are hallucination,memory decline,confusion of consciousness,epilepsy,sleep disorders,etc.Magnetic resonance imaging(MRI)can detect abnormal signals in the temporal lobe,and cerebrospinal fluid(CSF)often presents with normal or inflammatory changes.According to the different types of immunogen,AE can be divided into several types and each type can have specific clinical manifestations.Usually,AE antibodies are classified into two categories:one is anti-neuronal cell surface antigen antibodies,such as anti-N-methyl-D-aspartate(NMDA)receptor antibodies,leucine-rich glioma-inactivated protein 1(LGI1),gamma-aminobutyric acid B(GABAB)receptor antibodies,and anti-contactin-associated protein-like 2(CASPR2)receptor antibodies,anti-glycine receptor antibodies,etc.;the other is anti-Hu antibody,anti-Yo,Ri,Ma2,CV2,synaptic vesicles,glutamate decarboxylase(GAD)antibody,etc.CASPR2 is a cell adhesion molecule in axon protein family.It is expressed in axons of central and peripheral nervous system.It is the main target antigen of autoantibody of neuron voltage-gated potassium channel(VGKC)complex.Therefore,patients with positive anti-CASPR2 antibody may have symptoms of both central and peripheral nervous systems,such as neuromuscular rigidity,encephalitis,familial autonomic dysfunction,insomnia,neuropathic pain,etc.Researches have been focused on the clinical characteristics of different antibody types of AE in order to guide the clinical treatment.However,anti-CASPR2 antibody-associated encephalitis is rare,and there are few reports about the disease at home and abroad.There still lacks systematic understanding of the clinical characteristics of the disease.Study PurposeThe clinical data of 22 patients with anti-CASPR2 antibody-associated encephalitis were retrospectively analyzed.The clinical symptoms,laboratory data,imaging characteristics and video electroencephalogram(Video-EEG)manifestations of the patients were discussed with a purpose of better understanding of the clinical characteristics of the disease by systematic analysis.In particular,this data is helpful to understand the clinical characteristics of anti-CASPR2 antibody-associated encephalitis in China and to provide reference for the clinical diagnosis and treatment of this disease.Study Methods1.Study objects:Patients who were diagnosed with CASPR2 antibody associated encephalitis in the Affiliated Hospital of fifth and the First Affiliated Hospital from January 2017 to June 2019 were selected.The entry criteria were based on the diagnostic criteria of anti CASPR2 antibody associated encephalitis in 2017 from the expert consensus on diagnosis and treatment of autoimmune encephalitis in China.2.Clinical data analysis:The clinical manifestations,course of disease,laboratory data,imaging data,video-EEG results of the patients were systematically analyzed.Laboratory data include:biochemical,routine,immunoglobulin and virological tests of CSF;serum-related tests(including thyroid function,tumor markers,serum immunity,five anti-nuclear antibody profiles,anti-phospholipid syndrome-related antibodies);simultaneous detection of serum and CSF:autoimmune antibodies(including anti-LGI1,anti-NMDAR,anti-CASPR2,anti-AMPAR,anti-GABABR,anti-glutamate receptor,Oligoclonal bands,antineuronal antigen spectrum,etc.)Study Results1.Clinical manifestations:Seizures occurred in 18 cases(81.8%)during the course of the disease,and 16 cases had cognitive impairment(including poor memory,poor computing power,decreased orientation,attention,language ability,etc.)(72.7%),12 cases of mental symptoms(57.1%),7 cases of irritability,3 cases of hallucinations,3 cases of nonsense,abnormal cases of 2 cases,dizziness,dizziness,9 cases,sleep disorders(cases),limbs.Pain occurred in 8 cases(36.4%),poor eating in 4 cases(18.2%),headache in 4 cases(18.2%),fever in 3 cases(13.6%),autonomic nervous function symptoms in 4 cases(18.2%),including hyperhidrosis,panic,dyspepsia,chills and so on.2.Laboratory data:22 patients underwent lumbar puncture,and CSF was collected.The CSF pressure was measured at 100 to 270minH2O with a median of 182.5 mm H2O.The leucocyte number of CSF ranged from 0 to 12/L,with a median of 5/L;the total protein ranged from 0.14 to 0.59 g/L,with a median of 0.4 g/L;glucose ranged from 2.5 to 3.9 mmol/L,with a median of 3.02 mmol/L;and chlorine ranged from 112 to 130 mmol/L with a median of 126 mmol/L.All CSF patients were tested for virology and the results were negative.Twenty-two patients were tested for thyroid function and related antibodies.Twenty-one patients had normal thyroid function and one patient had low free triiodothyronine(FT3).Twenty cases(90.9%)were positive for anti-thyroglobulin antibodies(TGAb)and 14 cases(63.6%)were positive for thyroid peroxidase antibodies(TPO-Ab).Tumor markers were examined in all 22 patients and 12 cases(54.5%)were abnormal.22 patients received five serum immunization tests,the serum IgA level was higher than that of normal 18 cases(81.8%),the median was 10.75g/l;the serum IgG was higher than the normal 0 cases(0%),the median was 1.54g/l;the serum IgM was higher than the normal range 0 cases(0%),the median was 1.195g/l;the complement C3 was higher than the normal circumference 1 cases(4.5%),the median was 0.88g/l;the complement C4 was located in the normal range,and the median was 0.19g/l.Antistreptococcal hemolysin "O" antibodies were located in the normal range,the median was 45.3IU/ml;and the C reactive protein was elevated in 4 cases(18.2%)with a median of 5.875mg/l.All 22 patients underwent anti-phospholipid syndrome related tests:serum anticardiolipin antibody increased in 4 cases(18.2%)with a median of less than 10 RU/ml;anti-beta 2-glycoprotein 1 antibody increased in 6 cases(27.3%)with a median of 15 RU/ml;anti-neutrophil antibody spectrum was negative;serum anti-nuclear antibody spectrum was negative.Serum and CSF-CASPR2 antibodies were detected in 22 patients.Serum CASPR2 antibodies were positive in 22 patients(100%)and CSF-CASPR2 antibodies were positive in 10 patients(45.5%).Serum and CSF IgG index and oligoclonal bands were examined in 22 patients,of which 2 cases(9.1%)were positive for oligoclonal bands.22 patients underwent CSF immunoglobulin test:the CSF-IgA results were higher than the normal range in 19 cases(86.4%),the median was 0.27 mg/dl;the CSF-IgG value was higher than the normal range 0 cases(0%),the median was 2.89 mg/dl;the CSF-IgM value was higher than the normal range 0 cases(0%),the median was 0.075 mg/dl.Serum oligoclonal bands were detected in 22 patients and 2(9.1%)were positive.Antigen and antibody of neurons in serum and CSF were detected in all 22 patients.Anti-Hu antibody in serum was positive in 1 case and anti-Yo antibody in serum was positive in 1 case.3.Video-EEG:Video-EEG of 22 patients showed abnormalities in varying degrees,including diffuse slow wave;localized slow wave and epileptic wave in particular electrodes:4.Imaging:22 patients with anti-CASPR2 antibody-associated encephalitis underwent cranial CT examination,with abnormal signs(mainly low-density shadow in the lobe of the lesion)showed in 6 cases(27.3%).All 22 patients with anti-CASPR2 antibody-associated encephalitis underwent cranial magnetic resonance imaging(MRI).15 cases(68.2%)showed abnormalities.The main manifestations were unilateral,bilateral hippocampus or lobe lesions.Among them,11 cases(50%)had hippocampal lesions,8 cases(36.4%)had lobar lesions,and 4 cases(18.2%)had lobar and hippocampal lesions simultaneously.Four patients with anti-CASPR2 antibody-associated encephalitis underwent PET-CT examination,all of which indicated abnormalities.Three cases showed impaired glucose metabolism in lesions as revealed on MRI,among which one case showed increased glucose metabolism.Two cases showed no decreased glucose metabolism on brain areas with normal MR imaging.Conclusions1.Anti-CASPR2 antibody-associated encephalitis is a rare type of AE.When the main clinical manifestations are epilepsy,memory loss,psychiatric symptoms,sleep disorders,limb pain,headache,poor eating,fever and autonomic nervous function symptoms,it is necessary to consider the disease.Attention should be paid to identify other autoimmune diseases including anti-NMDAR-related encephalitis and anti-GABABR antibody-associated encephalitis,anti-LGI1 antibody encephalitis,etc.,especially when the peripheral nerve involvement such as limb pain,numbness,fascicular tremor,and myotonia occurs.2.In this study,we detected anti-CASPR2 antibodies in the sera of all the patients with anti-CASPR2 antibody-associated encephalitis,and some of them were positive in CSF.IgA was increased in the serum and CSF in most of the patients,and tumor markers were expressed in sera of half patients.The detection of serum thyroid function and related antibodies,C-reactive protein,ACL,?2-gpl-ab,antigens and antibodies in the serum and CSF nerve cells,auto immune brain antibodies,oligoclonal bands and immunoglobulins are helpful for the differential diagnosis of the disease.3.In this study,we found that diffuse slow wave,epileptic wave were the main changes in electroencephalogram in patients with CASPR2 antibody-related encephalitis.And localized slow wave was also commonly observed,but this lacked clinical significance.4.In this study,we found that the positive rate of anti-CASPR2 antibody-associated encephalitis on CT was low,and the main manifestation was low-density lesions in the lobes.In addition to the limbic system,brain lobe is more commonly involved on brain MRI.PET/CT revealed all possible lesions,most of which showed decreased glucose metabolism at the lesion site,while a few showed increased glucose metabolism at the lesion site.