Superficial white matter damage in anti-NMDA receptor encephalitis

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 89; no. 5; pp. 518 - 525
• Main Authors: Phillips, Owen Robert, Joshi, Shantanu H, Narr, Katherine L, Shattuck, David W, Singh, Manpreet, Di Paola, Margherita, Ploner, Christoph J, Prüss, Harald, Paul, Friedemann, Finke, Carsten
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.05.2018
• Subjects: Adult; Age; Anti-N-Methyl-D-Aspartate Receptor Encephalitis - complications; Anti-N-Methyl-D-Aspartate Receptor Encephalitis - pathology; Attention deficit hyperactivity disorder; Case-Control Studies; Cognitive Dysfunction - complications; Cognitive Dysfunction - pathology; Diffusion Tensor Imaging; Encephalitis; Female; Frontal Lobe - pathology; Humans; Hypotheses; Immunoglobulins; Male; Medical imaging; Memory; Neuroimaging; Neurology; Patients; Psychosis; Remission Induction; Schizophrenia; Temporal Lobe - pathology; Trends; White Matter - pathology; Young Adult
• ISSN: 0022-3050; 1468-330X; 1468-330X
• DOI: 10.1136/jnnp-2017-316822

BackgroundClinical brain MRI is normal in the majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter.MethodsForty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity.ResultsNon-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients.ConclusionsAnti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms.