Pathological Findings in Autoimmune Encephalitis Autopsy Specimens from Cases of Suspected Prion Disease
Hesham Abboud1, Christina Kerner2, Keisi Kotobelli2, Brian Appleby1, Mark Cohen1
1University Hospitals Cleveland Medical Center, 2Case Western Reserve University
Objective:
Our objective was to describe pathological findings of autoimmune encephalitis (AE) specimens submitted to the U.S. National Prion Disease Pathology Surveillance Center.
Background:
The underlying pathology of AE is not well characterized due to the limited opportunities to study tissue specimens. Autopsy specimens available at prion surveillance centers from patients with suspected Creutzfeldt-Jakob disease offer a unique opportunity to study the pathology of AE.
Design/Methods:
Pathology reports were obtained from the National Prion Center. Specimens negative for prion disease were screened for inflammatory pathology and those suggestive of AE were analyzed. Cases identified on autopsy were compared to institutional cases with fatal seronegative AE and available brain biopsy.
Results:
Between 1998 and 2022, 7934 specimens were evaluated of which 2998 (38%) were negative for prion protein. Querying the database for alternative diagnoses of encephalitis/encephalopathy yielded 43 cases that were screened by an experienced neuropathologist yielding 14 (0.5%) cases consistent with AE. Most specimens showed diffuse inflammation involving the limbic system (86%), basal ganglia (86%), cortex (71%), diencephalon (71%), and in some cases the brainstem (43%) and cerebellum (43%). Lymphocytic inflammatory infiltrate was predominantly perivascular with parenchymal extension in 64%. Microglial activation/nodules were seen in 64% of cases. Neuronal loss was present only in 50%. Pathological findings were identical to biopsy specimens from our institutional cohort.
Conclusions:
Seronegative AE may have consistent pathology with diffuse or multifocal perivascular inflammation and microglial activation. Half the patients do not have neuronal loss suggesting a potential for neurological recovery. The pathological distribution of inflammation seemed to exceed the typical radiological patterns of AE. These findings are preliminary and require further confirmation.