Clinical and Paraclinical Characterizations, Management, and Prognosis in DPPX Antibody-Associated Encephalitis: A Systematic Review

Abstract

In dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, DPPX antibodies from serum and CSF target the extracellular subunit of the voltage-gated potassium channel 4.2. This targeting leads to a characteristic clinical triad comprising gastrointestinal symptoms (predominantly diarrhea), cognitive-psychiatric dysfunction, and manifestations of CNS hyperexcitability, with hyperekplexia being a more specific feature. This rare disease typically presents with a subacute or chronic course and often affects middle-aged and older individuals. Patients may have a weak association with certain hematologic malignancies, particularly lymphoma and chronic lymphocytic leukemia. Brain MRI typically shows normal findings or nonspecific white matter changes. DPPX antibody-associated encephalitis responds well to immunotherapy, and most patients ultimately present with a good prognosis. However, relapses can occur. To improve our understanding of this rare but treatable autoimmune encephalitis and avoid misdiagnosis, we conduct a systematic review and summarize the current knowledge of its clinical and paraclinical features, management, and prognosis.

Figure 1. Flow Diagram of Article Selection Process for This Systematic Review

Figure 2. Clinical Presentations of DPPX Antibody-Associated Encephalitis

AQP4 = aquaporin 4; CASPR2 = contactin-associated protein-like 2; CRMP5 = collapsin response mediator protein 5; DPPX = dipeptidyl‐peptidase‐like protein 6; GAD = glutamic acid decarboxylase; GFAP = glial fibrillary acidic protein; NMDAR = N-methyl-d-aspartate receptor; T1DM = type 1 diabetes mellitus.

Figure 3. Representative Brain T2/FLAIR Axial MRI of 6 Patients With DPPX Antibody-Associated Encephalitis

(A) Mild T2/FLAIR hypersignals in the bilateral hippocampus. (B) T2/FLAIR hypersignals in the bilateral temporal lobe and hippocampus. (C) Mild T2/FLAIR hypersignals in the bilateral amygdala. (D) T2/FLAIR hypersignals in the right basal ganglia and thalamus. (E) T2/FLAIR hypersignals in the left centrum semiovale. (F) Extensive T2/FLAIR hypersignals in the bilateral frontal lobe and parietal lobe. Reprinted from Xiao et al., an open access article distributed under the terms of the Creative Commons CC BY license, which does not require permission for reuse. DPPX = dipeptidyl‐peptidase‐like protein 6; FLAIR = fluid-attenuated inversion recovery.