Metabolic features of encephalitis in patients with cognitive decline as revealed by brain FDG PET

Objectives Encephalitis can cause cognitive decline and atypical presentations of dementia, but establishing the diagnoses can be difficult. We examined cerebral metabolic features of encephalitis including rare antibody-mediated encephalitis.

Methods Patients with cognitive decline (age 22-67 yrs; 4 males) with final diagnoses (serum; CSF; and/or autopsy) of anti-NMDA receptor encephalitis (NMDA; n=3); anti-voltage-gated potassium channel encephalitis (VGKC; n=1); limbic encephalitis (LE; n=1); and Creutzfeldt-Jakob Disease (CJD; n=1) as well as representative probable Alzheimer’s disease (pAD; n=10) and normal controls (NC; n=35) were examined. Standard [F-18]FDG PET brain images were obtained and analyzed quantitatively using 3D-SSP Z-score maps with pons normalization compared to NCs.

Results Compared to NCs, anti-NMDA encephalitis patients showed hypometabolism involving medial (Z>4) and lateral (Z>4) occipital cortices and cerebellum (Z>3). All cases showed variable involvement of fronto-parieto-temporal association cortices (Z=2-5). Anti-VGKC encephalitis showed milder thalamic and brainstem hypometabolism (Z=2-3) while LE showed distinct 'hypermetabolism' in the medial temporal cortex (Z>7). CJD showed asymmetric hypometabolism involving both primary and association cortices. Posterior cingulate cortex (Z>3) was involved in CJD, LE, and one NMDA case. Compared to pAD cases, in which known hypometabolism in parieto-temporal and frontal association cortices (Z=3-6) with sparing of primary cortices was seen, encephalitis cases exhibited involvement of primary cortices and subcortical structures.

Conclusions Differential involvements of cortical and subcortical structures that were distinct from pAD were seen in various encephalitis cases. These metabolic features could potentially assist in the differential diagnoses of patients with cognitive decline. Regional vulnerability of altered brain metabolism associated with encephalitis warrants further mechanistic investigations.

Research Support NIH/RO1NS04525