| BackgroundAutoimmune encephalitis(AE)is one of newly identified neurological autoimmune diseases with cognitive and mental behavioral abnormalities as its main manifestations.It is divided into different subtypes depending on the antigen target,of which the anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is the most common type of AE.Previous study of case series have found that AE responds well to immunotherapy however with limited effect and some patients remain with varying severity of disability.Therefore,individualized treatment protocols based on disease severity may be of greatest benefit to patients.PurposeTo analyze the relationship between the maintenance protocols of immunotherapy and anti-epileptic treatment and clinical outcomes in patients with anti-NMDAR encephalitis of different imaging results.MethodIn this study,we collected data of anti-NMDAR encephalitis cases diagnosed in Qilu Hospital of Shandong University in the past 5 years,and divided them into positive group(M group)and negative group(N group)according to whether there were positive cranial magnetic resonance imaging(MRI)findings associated with this disease.Follow-up was performed to analyze the relationship between the maintenance protocols of immunotherapy and anti-epileptic treatment and the long-term prognosis of patients in both groups.ResultA total of 94 confirmed cases were finally included in this study,finding that younger females were more common,with a median age of 18 years(1-80 years)and a male-to-female ratio of 41:53.Cranial MRI was performed in all patients,and abnormal signal lesion and/or cortical atrophy were seen in 35 cases(37.23%),which were divided into the MRI-positive(M)group,while the other 59 cases(62.77%)were divided into MRI-negative(N)group.The main clinical manifestations included seizures(81.91%),psychiatric abnormalities(76.60%),motor disorders(59.57%),unfavorable speech(56.38%),disorders of consciousness(52.13%),and impaired memory(43.62%),with varying degrees of severity.The Clinical Assessment Scale in Autoimmune Encephalitis(CASE)values ranged from 1 to 26(median 9),and the modified Rankin Scale(mRS)scores ranged from 1 to 5(median 3).Among them,there were 77 cases with seizures during the acute phase,of which 63(81.82%)presented with generalized or partial secondary generalized seizures,and 38(49.35%)developed status epilepticus.There was no significant difference in the clinical manifestations.and severity of the acute phase between the two groups(P>0.05).Of the ancillary findings,hyponatremia was found in 16 cases(17.02%),increased cell number and protein concentration in cerebrospinal fluid were respectively seen in 58 cases(61.70%)and 26 cases(27.66%),and the positive rate of Group M exceeded Group N.Electroencephalography found abnormalities in 63 patients(88.73%),which generally showed unspecific slow waves and some captured typical epileptic discharges;3(4.23%)patients found extreme δ brushes which was disease-specific.60 cases were routinely screened for tumors,of which 10 had definitely found space occupying lesions and 8 were proven to be tumors by imaging or biopsy(13.33%,7 were ovarian teratomas,1 of which was immature teratoma),independent of MRI findings(χ2=0.296,P=0.33).All patients had been tested to find at least one "+" titer of NMDAR antibodies in cerebrospinal fluid and/or serum,of which anti-contactin-associated protein-like 2(CASPR2)antibodies was tested in 2 cases as well.Demyelinating antibodies were detected in cerebrospinal fluid and/or serum of 14 patients,all of which were negative.35 patients were examined for paraneoplastic antibodies and one case was found to be positive for serum anti-CV2 antibody and another case was serum anti-paraneoplastic antigen Ma2(PNMA2)antibody.There was no significant difference in antibody results of two groups(P>0.05).After a follow-up period of 4 to 73 months(median 31),5(5.32%)patients died,of which 1 died from suicide,1 from asphyxia due to seizures,and 3 from respiratory failure due to pulmonary infections(1 of which was the complication of seizure);18(19.15%)experienced recurrence,which could be manifested as aggravation of the existing symptoms or the appearance of new symptoms such as headache,memory impairment,motor symptoms,psychiatric symptoms,etc.8 cases(8.51%)had relapsed for two or more times.By the time of the final follow-up,the overall prognosis of the patients was good,with 49 cases(52.13%)free of any residual symptoms and 74 cases(78.72%)not affecting daily life(final mRS<2).Common residual symptoms included seizures(19 cases,21.35%),impaired memory(18 cases,20.22%),motor disorders(12 cases,13.48%),psychiatric abnormalities(9 cases,10.11%),and unfavorable speech(8 cases,8.99%).Notably,the prognosis was significantly worse in the group M than in the group N(χ2=9.574,P=0.002,OR[95%CI]:3.948[1.620-9.621]).In group N,38 patients(64.41%)had a good symptomatological prognosis,and the recurrence rate was only 11.84%,with no significant difference between short-term(course<6 months)and long-term(course≥6 months)immunotherapy(χ2=0.517,P=0.472,OR[95%CI]:1.481[0.506-4.334]).In group M,10 patients(28.57%)had at least once relapse and 24 patients(68.57%)developed a poor symptomatological prognosis so that they needed to maintain a long-term(duration ≥6 months)immunotherapy regimen(P=0.035,OR[95%CI]:0.159[0.028-0.899]).In addition,the majority(74.03%)of the 77 patients with seizures in the acute phase were free of epilepsy,while MRI-positive patients with seizure events had a worse epileptic prognosis(χ2=5.029,P=0.025,OR[95%CI]:3.250[1.132-9.330])and may require longer maintenance of anti-epileptic drugs(≥1 year,P=0.010).ConclusionAnti-NMDAR encephalitis is the most common type of autoimmune encephalitis,more commonly seen in young women in clinical practice.The acute phase is mostly characterized by seizures and cognitive and psychiatric behavioral abnormalities in varying degrees of severity.More than a third of the patients have lesion of abnormal signal and/or cortical atrophy on the cranial MRI.Extreme δ brushes found on EEG may be a characteristic change in anti-NMDAR encephalitis.In young women,anti-NMDAR encephalitis is often associated with ovarian teratomas,for which early tumor-screening and removal of the cause is essential for disease outcome.Autoimmune encephalitis may be overlaid with demyelinating disease and paraneoplastic syndromes as well,which should be identified and screened as soon as possible.Anti-NMDAR encephalitis patients generally have a good prognosis,but there are still some residual neurological defects,affecting the quality of patients’ life of.As a routine ancillary diagnostic technique for this disease,cranial MRI findings mostly show negative results and have no correlation with the clinical features in the acute phase,but can help to guide individualized treatment regimens for patients with NMDAR encephalitis.Patients with disease-responsible lesions identified by cranial MRI have a relatively poor prognosis and should be maintained on a longer-term immunotherapy and antiepileptic treatment. |
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