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

Abstract

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.

Case report: Autoimmune encephalitis associated with anti-CASPR2 antibody mimicking cerebral infarction

“…One previous study reported that a CASPR2 antibody serum titer cut-off at ≥ 1:200 had a diagnostic sensitivity of 85% and a specificity of 81% (14). Notably, such a titer of 1:10 has been reported in previous studies in patients with anti-CASPR2 antibody encephalitis (9,17). Specifically, one study described two patients with this disease with prominent brainstem lesions seen on MRI.…”

“…Specifically, one study described two patients with this disease with prominent brainstem lesions seen on MRI. These two patients had full or partial neurological recovery after immunotherapy ( 17 ). In another study, unfortunately, the authors did not provide detailed information about the patients with titers of 1:10 (9).…”

“…Studies based on MRI and positron emission tomography have identified the medial temporal lobe as the part of the central nervous system most vulnerable to anti-CASPR2 antibodies ( 6 , 8 , 9 , 14 , 15 ). However, some cases of abnormalities have been reported in the frontal, parietal, and occipital lobes, brainstem, cerebellar regions, basal ganglia, and the insula ( 6 , 9 , 16 , 17 ). Frontal lobe lesions have been detected by positron emission tomography in a 22-year-old woman with systemic lupus erythematosus ( 18 ) and a 61-year-old man without systemic disease ( 19 ), neither of whom showed abnormal brain MRI.…”

“…Frontal lobe lesions have been detected by positron emission tomography in a 22-year-old woman with systemic lupus erythematosus ( 18 ) and a 61-year-old man without systemic disease ( 19 ), neither of whom showed abnormal brain MRI. Another case of anti-CASPR2 antibody-associated autoimmune encephalitis showed abnormal T2-weighted hyperintense patchy lesions without restricted diffusion in the subcortical white matters of the frontal lobe, which showed patchy or ring-like enhancement on contrast-enhanced T1-weighted MRI ( 17 ). The present patient did not show lesions in the medial temporal lobe by either CT or MRI.…”

“…The mechanisms responsible for the different propensity of involved brain regions in the current literature remain unclear. In a previous case of anti-CASPR2 encephalitis with involvement of the brainstem, the authors suggested that the predominant exposure of antigenic epitopes in the brainstem may have facilitated the preferential binding of anti-CASPR2 IgG1 to the target self-antigens and triggered subsequent pathogenic cascades ( 17 ). A previous study on anti-GABA A receptor encephalitis reported that the topology of MRI lesions might be associated with the distribution of β3 subunit-containing GABA A receptors and reflected the patients’ disease severity and outcomes ( 20 ).…”