Clinical and imaging analysis to evaluate the response of patients with anti-DPPX encephalitis to immunotherapy

Abstract

Background: To report the main spectrum, new clinical and imaging characteristics of dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, and evaluate the effect of immunotherapy.Methods: A retrospective analysis of nine patients reported describing the clinical and immunological features was performed, and all previously reported cases were reviewed. A cell-based indirect immunofluorescence assay with human embryonic kidney 293 cells transfected with DPPX was used. Results: Nine patients were identified (median age, 51 years; range, 14–65 years) with prodromal fever, diarrhea, or weight loss, followed by a rapidly progressive encephalopathy characterized by cognitive disorder. One patient who received methylprednisolone therapy and a trail of tacrolimus showed substantial improvement and had no relapse in the six-month follow-up. Our comprehensive literature review demonstrated that a total of 53 cases were reported, of which more than half had prodromal weight loss (52.8%), and gastrointestinal disorders (58.5%). Cognitive (74.6%) and brainstem/spinal cord disorders (75.5%) were the most common major symptoms. Our study is the first to report three patients with anti-DPPX encephalitis who had sleep disorder of rapid eye movement sleep behavior disorder (RBD), limb paralysis (two), severe pleocytosis and elevated protein levels (two) in the cerebrospinal fluid, and increased T2/FLAIR signal abnormalities in the bilateral hippocampus, temporal lobe, amygdala, basal ganglia, thalamus, centrum semiovale, and frontal and parietal lobes in seven cases (77.8%).Conclusion: Our study expanded the clinical and imaging phenotype of anti-DPPX- encephalitis. We also reported the use of tacrolimus for long-term immunosuppressant therapy in anti-DPPX encephalitis, with substantial improvement and no relapse during a follow-up period of 6 months. Further studies elucidating the entire clinical spectrum of anti-DPPX encephalitis, pathogenic roles, and prognosis under long-term immunosuppressive therapy are warranted.

Clinical Reasoning: A 37-Year-Old Man With Involuntary Movements, Gait Disturbance, and Hyperesthesia

“…This includes corticosteroids, although maintenance with tacrolimus, rituximab, IVIg and PLEX have also been used. 7,8,14…”

“…5,9 Postural hypotension and sleep disturbances have also been reported. 7 Hyperexcitability in the central and peripheral nervous systems are reported to cause seizures, 7 pruritus, 10 and dysesthesias. 8 Patients may occasionally present with a picture similar to progressive encephalomyelitis with rigidity and myoclonus (PERM) or stiff-person syndrome.…”

“…This includes corticosteroids, although maintenance with tacrolimus, rituximab, IVIg and PLEX have also been used. 7,8,14 In one review of 53 patients, 48% experienced marked improvement after immunotherapy. 7 Cessation of therapy led to relapse of symptoms in 2 of 9 patients in a small case series.…”

Update in autoimmune and paraneoplastic myelopathies: Newly described antigen targets and antibody testing

“…Anti-DPPX is a cell-surface antibody typically seen in syndromes with features of central nervous system hyperexcitability (e.g., psychiatric symptoms, seizures, tremors, hyperkplexia, myoclonus), memory loss and significant weight loss with or without diarrhea (36)(37)(38)(39). Additional features include movement disorders, sleep disorders resembling REM-sleep behavior disorder, dysautonomia, cerebellar ataxia, and brainstem and spinal cord disorders.…”

“…Additional features include movement disorders, sleep disorders resembling REM-sleep behavior disorder, dysautonomia, cerebellar ataxia, and brainstem and spinal cord disorders. In a review of 53 patients, brainstem or spinal cord disorders were seen in 75.5% of cases, with symptoms including eye movement abnormalities, dysarthria, dysphagia, stiffness, respiratory failure, vertigo, and hyperekplexia (36). In another cohort of 20 patients, 15 had brainstem or spinal cord disorders (39).…”