Neuropathological Variability within a Spectrum of NMDAR-Encephalitis

Area of Science:

• Neuropathology
• Neuroimmunology
• Autoimmune Encephalitis

Background:

• N-methyl-D-aspartate receptor (NMDAR)-encephalitis is a severe autoimmune neurological disorder.
• Understanding its neuropathological underpinnings is crucial for diagnosis and treatment.

Purpose of the Study:

• To characterize the neuropathological features of N-methyl-D-aspartate receptor (NMDAR)-encephalitis.
• To examine the impact of comorbidities on neuropathology in a cohort of archival autopsy cases.

Main Methods:

• Analysis of four archival autopsy cases of N-methyl-D-aspartate receptor (NMDAR)-encephalitis.
• Histopathological examination including immunohistochemistry for inflammatory cells and markers.
• Correlation of neuropathological findings with clinical data and disease severity.

Main Results:

• Inflammatory infiltrates (T cells, B cells/plasma cells) were observed in basal ganglia, amygdala, and hippocampus in untreated cases.
• Decreased NMDAR immunoreactivity in the hippocampus correlated with disease severity.
• Co-occurring pathologies like PTLD and demyelination altered inflammatory distribution and characteristics.

Conclusions:

• The topographic distribution of inflammation in NMDAR-encephalitis aligns with clinical symptoms.
• Loss of NMDAR immunoreactivity is a key neuropathological correlate of disease severity.
• Comorbidities significantly influence the neuropathological presentation and intensity of inflammation in NMDAR-encephalitis.