Anti-adenylate kinase 5 encephalitis: Case series and review of ¹⁸F-DPA714 PET/MRI radiographic changes

Anti-adenylate kinase 5 (AK5) encephalitis is a rare, predominantly limbic autoimmune disorder featuring subacute cognitive and psychiatric decline. Given the limited literature and MRI's suboptimal sensitivity to neuroinflammation, often precluding timely therapeutic escalation, we sought to delineate the clinical and multimodal imaging spectrum of this condition and propose stage-specific management protocols.

Two female patients (aged 15 and 65 years) with subacute cognitive and psychiatric-behavioral disturbances were prospectively evaluated with serial MMSE, CASE and mRS clinical assessments at symptom onset and follow-up. All patients received intravenous methylprednisolone and immunoglobulin, with rituximab administered in one of the cases. Serum and CSF were tested for anti-AK5 antibodies using CBA and TBA. Brain MRI and ¹⁸F-DPA714 PET/MRI were performed to assess structural and microglial activation and aggregation patterns.

Both patients exhibited prominent anterograde amnesia, psychiatric manifestations, and sleep disturbances. Anti-AK5 antibodies were detected in the serum of both patients via CBA at titers of 1:100 and 1:30, respectively. MRI demonstrated bilateral hippocampal/temporal lobe atrophy with mild T2/FLAIR hyperintensities. ¹⁸F-DPA714 PET/MRI revealed increased tracer uptake in the brainstem, frontal, occipital, and hippocampal regions. After intravenous methylprednisolone and immunoglobulin, with rituximab, the adolescent patient showed marked clinical and cognitive recovery (MMSE: 18 to 28; CASE: 6 to 0 in one year). Conversely, the older patient demonstrated limited improvement, with persistent amnesia and neuropsychiatric symptoms.

This case series defines the clinical spectrum of anti-AK5 encephalitis, supporting ¹⁸F-DPA714 PET/MRI for detecting neuroinflammation correlating with clinical manifestations. Adjunctive CD20-targeted therapy showed efficacy in one patient, warranting B-cell immunotherapy research in larger cohorts.