Anti-N-methyl-D-aspartate receptor encephalitis: an emerging cause of centrally mediated sinus node dysfunction

Abstract

Aims: Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) is a recently recognized form of autoimmune encephalitis that typically affects young women, often as a paraneoplastic syndrome related to ovarian teratoma. Clinical features include psychiatric and neurological disturbances, central hypoventilation, autonomic instability, and cardiac dysrhythmias. The prevalence, nature, and outcomes of cardiac dysrhythmias in patients with NMDARE have not been well described.

Methods and results: Records of 10 consecutive patients with NMDARE were reviewed to obtain clinical, laboratory, echocardiographic, electrocardiographic, and radiological data. Patients were all female with an average age of 23 ± 5.5 years. Echocardiograms revealed structurally normal hearts with the exception of mild left ventricular hypertrophy in two cases. Eight patients had inappropriate sinus tachycardia. Six patients developed significant sinus bradycardia, which included periods of sinus arrest in four cases. Five patients manifested both sinus bradycardia and tachycardia. Bradycardia was often triggered by identifiable vagal stimuli. Temporary pacing was instituted in three patients, but permanent pacing was not required in any of the patients. Magnetic resonance imaging (MRI) scans revealed mesial temporal abnormalities in nine patients. In all cases, the dysrhythmias resolved with treatment of the underlying immune disorder with immunotherapy and/or teratoma resection. There was no evidence of dysrhythmia recurrence in any patient at follow-up.

Conclusion: Anti-N-methyl-D-aspartate receptor encephalitis is a recently recognized cause of autoimmune encephalitis with a predilection to cause severe sinus node abnormalities. Temporary pacing is occasionally required, but permanent pacing appears to be unnecessary. An analysis of the clinical syndrome coupled with MRI and experimental data may offer insight into central mechanisms of heart rate regulation.

Figure 1

Examples of sinus bradycardia and sinus arrest in Anti-N-methyl-d-aspartate receptor encephalitis. Recordings demonstrating sinus bradycardia and sinus arrest in two patients: Examples A and B—Patient 3, C—Patient 4. In example B, sinus arrest is preceded by slowing of the sinus rate and by atrio-ventricular block. The paper speed is 25 mm/s.

Figure 2

Brain magnetic resonance imaging findings in Anti-N-methyl-d-aspartate receptor encephalitis. T2-weighted images from three patients in this series, showing reversible magnetic resonance imaging T2 signal changes in grey matter. In Patient A, there is only an abnormal, bilateral increase in mesial temporal T2-weighted signal. Patient B had similar temporal signal changes, but also left parietal cortical abnormalities. Patient C had little temporal lobe abnormality (sections not shown), but multiple areas of frontal and parietal gyral signal change.