Clinical Character of CASPR2 Autoimmune Encephalitis: A Multiple Center Retrospective Study

Abstract

ObjectiveTo examine the clinical characteristics of autoimmune encephalitis associated with the contactin-associated protein-2 (CASPR2) antibody.Materials and MethodsMedical records of all patients diagnosed with CASPR2 antibody-associated encephalitis were retrospectively analysed. Data regarding demographic features, neurological symptoms and signs, laboratory tests, imaging results, treatments, and prognosis were collected.ResultsA total of 25 patients aged from 3 to 79 years old were enrolled in this study, with a median age of 43. Eight of 25 (32%) were female, and 17 of 25 (68%) were male. The median age of symptom onset was 42 years old with the course of disease from onset to hospital admission ranging from 2 days to 6 months (median was 17 days). Six patients (6/25) had fever as an onset symptom. During the course of disease, cognitive disturbance was the most common symptom, which was observed in 17 patients (17/25) in total. Eight patients (8/25) met the criteria for limbic encephalitis. Epileptic seizure occurred in six of these eight patients. Four patients (4/25) were diagnosed as Morvan syndrome. All patients were positive for anti-CASPR2 antibody in the serum (1:10–1:300). In six patients, antibodies were detected both in the blood and CSF (1:32–1:100). White blood cell (WBC) counts in the CSF were elevated in eight patients (8/25). The concentration of proteins in CSF increased in 10 patients (ranging from 480 to 1,337.6 mg/dl), decreased in seven patients (ranging from 23.2 to 130.5 mg/dl) and remained at a normal range in the other eight patients (ranging from 150 to 450 mg/dl). Abnormal electroencephalogram (EEG) activities included slow background activity and epileptic patterns. Abnormal signals in the bilateral hippocampus were detected by magnetic resonance imaging (MRI) in three patients presenting cognitive disturbance. In one patient who had limbic encephalitis, increased metabolism of bilateral basal ganglia and the mesial temporal lobe was revealed by PET-CT. Eleven of 15 patients receiving immunotherapy experienced varying degrees of improvement. Relapse occurred in four of 25 patients (4/25) after 2 months.ConclusionCASPR-antibody-mediated autoimmune encephalitis is characterized by diverse clinical manifestations. The most prominent conclusion revealed by this retrospective analysis is the involvement of both central and peripheral nerve systems, as well as a lower relapse rate, a good response to immunotherapy, and favorable short-term prognosis after treatment was also demonstrated. Besides, additional work is necessary to evaluate the long-term prognosis.

Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis

“…Similar imaging findings have been demonstrated in a recent multicenter cohort study conducted in a Chinese population, in which the medial temporal lobe or hippocampus can be affected unilaterally or bilaterally (18). In addition, regional hypometabolism or hypermetabolism in the medial temporal lobes or basal ganglia was revealed by fluorodeoxyglucose positron emission tomography (FDG-PET), also indicating the involvement of these regions (4,18). Inconsistent with previous studies, brain MRI did not find remarkable lesions in the medial temporal lobes of the present two patients; instead, multifocal lesions involving white and gray matters were noted in other regions, particularly in the brainstem.…”

“…Of these, 67 (42.1%) presented with encephalitis or T2 hyperintensities in the medial temporal lobes, occupying the first place of the affected CNS regions in anti-CASPR2 antibody-associated autoimmune encephalitis ( 4 ). Similar imaging findings have been demonstrated in a recent multicenter cohort study conducted in a Chinese population, in which the medial temporal lobe or hippocampus can be affected unilaterally or bilaterally ( 18 ). In addition, regional hypometabolism or hypermetabolism in the medial temporal lobes or basal ganglia was revealed by fluorodeoxyglucose positron emission tomography (FDG-PET), also indicating the involvement of these regions ( 4 , 18 ).…”

“…Robust imaging evidence reveals that the medial temporal lobe is the most vulnerable CNS region associated with anti-CASPR2 antibodies ( 4 , 15 , 17 , 18 ). In a review enrolling 667 patients with anti-CASPR2 antibody-associated disorders, 299 received MRI scans and abnormal CNS lesions were reported in 159 cases.…”

Clinical Features and Outcomes in Pediatric Autoimmune Encephalitis Associated With CASPR2 Antibody

“…The fact that antibodies against VGKC-complex can lead to autoimmune encephalitis was confirmed (7 (2,7,9). The proportion of autoimmune encephalitis and peripheral nervous system involvement is lower in children compared to adults.…”

“…The recurrence rate of anti-N-methyl-D-aspartate receptor encephalitis was ranged from 12 to 29% (18). Approximately 16-37.5% of patients with positive anti-CASPR2 antibody experienced a relapse 2 months to several years months after the first episode (7,9,15). In one study, half of the recurrence cases were not treated appropriately in the first episode.…”