The Cerebrospinal Fluid And Clinical Features Of 62 Patients With Anti-n-methyl-d-aspartate Receptor Encephalitis

Background and objectiveAnti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is a type of autoimmune encephalitis characterized by the anti-NMDAR antibody positive,which has been discovered in recent years.The disease is more common in young women,often acute or subacute onset,with prodromal symptoms such as headache or fever.Common clinical features include a change in behavior,psychosis,seizures,memory and cognitive deficits,abnormal movements,a decreased level of consciousness,central hypoventilation and autonomic dysfunction.In 2016,Graus and Dalmau’s diagnostic criteria for autoimmune encephalitis pointed out that in view of the fact that antibody testing is not readily accessible in many hospitals and results can take several weeks to obtain,clinicians should try their best to make early diagnosis based on clinical symptoms and routine cerebrospinal fluid testing and give earlier immunotherapy to improve outcome of patients.At present,there are some studies about the abnormal manifestations and changes of Cerebrospinal fluid(CSF)in patients with anti-NMDAR encephalitis.A study found that CSF abnormalities are not associated with patient outcomes.Other study found that the abnormal rate of cerebrospinal fluid in patients with anti-NMDAR encephalitis in Chinese population was lower than that reported in foreign countries.CSF abnormallities in early stage of anti-NMDAR encephalitis mainly present with elevated WBC counts,while in middle and late clinical courses,predominately,intrathecal IgG synthesis increased and oligoclonal bands was positive.The relationship between brain MRI,clinical symptoms and cerebrospinal fluid has not been reported.Therefore,this study analyzes the relationship between brain MRI,clinical symptoms and cerebrospinal fluid by analyzing the CSF and clinical features of 62 patients with anti-NMDAR encephalitis to provide a reference for early diagnosis of anti-NMDAR encephalitis Materials and MethodsThis study collected the clinical data of 62 patients with anti-NMDAR encephalitis diagnosed from the First Affiliated Hospital of Zhengzhou University from October 2016 to October 2018.According to the criteria for the diagnosis of anti-NMDAR encephalitis proposed by Graus and Dalmau in 2016,the rapid progression time of the disease was defined as 3 months and the lumbar puncture time at the anti-NMDAR antibody-positive of cerebrospinal fluid was the duration of the disease.The study was grouped according to the disease duration.The disease duration <1 month was defined as the early stage of the disease and the disease duration >1 month was defined as the middle and late stage of the disease.The CSF cytology,biochemistry,immunoelectrophoresis and other indicators were analyzed.According to the abnormality of the brain MRI,it was divided into abnormal group and normal group.The CSF cytology and biochemistry were analyzed.Finally,the characteristics of cerebrospinal fluid in patients with seizure as the initial symptom were analyzed.ResultsIn 62 patients,26 cases were male and 36 female cases,male: female =1:1.3,age from 12 to 83 years old,the mean age was 34.29 years old,the median age was 32 years old and the peak incidence was 25 to 35 years old.48 patients(77.42%)were under 45 years old.9 patients(14.5%)were younger than 18 years old.In 62 patients,34 patients(54.83%)had non-specific prodromal symptoms,33 patients had fever or headache and 1 patient had diarrhea.The common initial symptoms include a change in behavior and psychosis(30.64%),seizures(22.58%),cognitive dysfunction(16.13%)and decreased levels of consciousness(9.7%),other focal neurological symptoms.The main clinical symptoms in the course of the disease include a change in behavior and psychosis(83.8%),seizures(72.58%),cognitive dysfunction(32.26%),decreased levels of consciousness(16.13%).In 62 patients,intracranial pressure increased in 24 patients(45.16%)and 12 patients(50%)had mild increase in intracranial pressure and intracranial pressure decreased in 4 patients(1.6%).41 patients(66.12%)had increased CSF white blood cell count,53 patients(85.5%)had increased lymphocyte ratio,neutrophils were positive in 24 patients(38.70%).Total protein concentration increased in 20 patients(32.25%)and total protein concentration decreased 1 patient(1.6%).Serum and cerebrospinal fluid immunoelectrophoresis were tested in 46 patients.CSF albumin increased in 16 patients(34.78%),CSF globulin increased in 17 patients(36.95%).Alb quotient increased in 7 patients(15.21%),intrathecal IgG synthesis increased in 35 patients(76.08%),IgG generation index elevated in 32 patients(69.56%),24-hour CSF IgG synthesis rate increased in 22 patients(47.82%),CSF oligoclonal zone was positive in 7 patients(15.21%),only 1 patient(1.6%)is completely normal.Anti-NMDAR antibodies of CSF was tested in 62 patients and Anti-NMDAR antibodies of serum was tested in 25 patients at the same time.Anti NMDAR antibody of CSF was positive in 62 patients(100%)and anti NMDAR antibody of serum was positive in 12 patients(48%).24 patients were tested for Anti-neuronal intracellular antigen antibody in CSF,anti-neuronal intracellular antigen antibody is negative in 23 patients(95.83%)and anti-Yo antibody is positive in 1 patient(4.17%).Virus antibody in CSF was tested in 49 patients,virus antibody is negative in 47 patients(95.91%)and 2 patients were positive.In 62 patients,32 patients(51.6%)had brain MRI abnormalities,which may involve the frontal lobe,parietal lobe,temporal lobe,hippocampus,thalamus,insula,lateral ventricle,basal ganglia and corpus callosum.14 patients underwent MRI-enhanced scanning,5 patients showed dural or pia mater enhancement,5 patients showed local enhancement and 4 patients showed no abnormal reinforcement.In 62 patients,the proportion and concentration of CSF total protein abnormalities in the early stage group were significantly higher than those in the middle and late group(P<0.05).There was no significant difference in other indicators of cerebrospinal fluid cytology and biochemistry(P>0.05).Serum and CSF immunoelectrophoresis were detected in 46 patients.There was no significant difference in immunoelectrophoresis of CSF between the early stage group and the middle and late group(P>0.05).The total protein concentration in the abnormal brain MRI group was significantly higher than that in the normal MRI group(P<0.05),there was no significant difference in other indicators of cerebrospinal fluid cytology and biochemistry(P>0.05).Seizure presents as the initial symptom in 14 patients,age ranges from 15 to 62 years old and the average age was 32.57 years old,including 11 males(78.57%)and 3 females(21.42%).9 patients(64.28%)had prodromal symptoms.Characteristics of CSF: white blood cell count increased in 7 patients(50%),lymphocyte ratio increased in 11 patients(78.58%)and total protein concentration increased in 4 patients(28.57%).In 12 patients with CSF and serum paired immunoelectrophoresis: cerebrospinal fluid globulin increased in 7 patients(58.3%),IgG generation index increased in 8 patients(66.67%),24 hours CSF IgG synthesis rate increased in 6 patients(50%),CSF oligoclonal band is positive in 1 patient(8.3%),Alb value increased in 3 patients(25%).Except that anti-NMDAR antibody is positive,only 1 patient is normal in CSF cytology,biochemical and immunoelectrophoresis.Conclusion1.Anti-NMDAR encephalitis is more common in young women,with prodromal symptoms of headache or fever,the main clinical symptoms include a change in behavior,psychosis,seizures,cognitive dysfunction and other symptoms.2.If they had headache or fever before onset,seizure presenting as the initial symptom in male patients has a suggestive significance for anti-NMDAR encephalitis.3.In anti-NMDAR encephalitis,lumbar puncture,intracranial pressure,white blood cell count,lymphocyte ratio,total protein concentration mainly mildly increased,neutrophils were positive and the total protein of CSF is elevated in the middle and late stages of anti-NMDAR encephalitis.4.In anti-NMDAR encephalitis,the sensitivity of anti-NMDAR antibody testing is higher in CSF than in serum,Anti-multiple neuron antibodies,virus antibodies may be positive.5.Brain MRI abnormality with anti-NMDAR encephalitis is related to the total protein concentration of CSF,which may be related to the duration of the disease.